1.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
2.
Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
3.
Three-dimensional space
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Three-dimensional space is a geometric setting in which three values are required to determine the position of an element. This is the meaning of the term dimension. In physics and mathematics, a sequence of n numbers can be understood as a location in n-dimensional space, when n =3, the set of all such locations is called three-dimensional Euclidean space. It is commonly represented by the symbol ℝ3 and this serves as a three-parameter model of the physical universe in which all known matter exists. However, this space is one example of a large variety of spaces in three dimensions called 3-manifolds. Furthermore, in case, these three values can be labeled by any combination of three chosen from the terms width, height, depth, and breadth. In mathematics, analytic geometry describes every point in space by means of three coordinates. Three coordinate axes are given, each perpendicular to the two at the origin, the point at which they cross. They are usually labeled x, y, and z, below are images of the above-mentioned systems. Two distinct points determine a line. Three distinct points are either collinear or determine a unique plane, four distinct points can either be collinear, coplanar or determine the entire space. Two distinct lines can intersect, be parallel or be skew. Two parallel lines, or two intersecting lines, lie in a plane, so skew lines are lines that do not meet. Two distinct planes can either meet in a line or are parallel. Three distinct planes, no pair of which are parallel, can meet in a common line. In the last case, the three lines of intersection of each pair of planes are mutually parallel, a line can lie in a given plane, intersect that plane in a unique point or be parallel to the plane. In the last case, there will be lines in the plane that are parallel to the given line, a hyperplane is a subspace of one dimension less than the dimension of the full space. The hyperplanes of a space are the two-dimensional subspaces, that is
4.
Protein structure
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Protein structure is the three-dimensional arrangement of atoms in a protein molecule. Proteins are polymers — specifically polypeptides — formed from sequences of amino acids, a single amino acid monomer may also be called a residue indicating a repeating unit of a polymer. Proteins form by amino acids undergoing condensation reactions, in which the amino acids lose one water molecule per reaction in order to attach to one another with a peptide bond. By convention, a chain under 30 amino acids is often identified as a peptide, to understand the functions of proteins at a molecular level, it is often necessary to determine their three-dimensional structure. Protein structures range in size from tens to several amino acids. By physical size, proteins are classified as nanoparticles, between 1–100 nm, very large aggregates can be formed from protein subunits. For example, many thousands of actin molecules assemble into a microfilament, a protein may undergo reversible structural changes in performing its biological function. The alternative structures of the protein are referred to as different conformational isomers, or simply, conformations. There are four levels of protein structure. Each α-amino acid consists of a backbone that is present in all the amino acid types, an exception from this rule is proline. Because the carbon atom is bound to four different groups it is chiral, glycine however, is not chiral since its side chain is a hydrogen atom. A simple mnemonic for correct L-form is CORN, when the Cα atom is viewed with the H in front, the primary structure of a protein refers to the linear sequence of amino acids in the polypeptide chain. The primary structure is held together by covalent bonds such as peptide bonds, the two ends of the polypeptide chain are referred to as the carboxyl terminus and the amino terminus based on the nature of the free group on each extremity. Counting of residues always starts at the N-terminal end, which is the end where the group is not involved in a peptide bond. The primary structure of a protein is determined by the corresponding to the protein. A specific sequence of nucleotides in DNA is transcribed into mRNA, the sequence of amino acids in insulin was discovered by Frederick Sanger, establishing that proteins have defining amino acid sequences. The sequence of a protein is unique to that protein, and defines the structure, the sequence of a protein can be determined by methods such as Edman degradation or tandem mass spectrometry. Often, however, it is directly from the sequence of the gene using the genetic code
5.
Peptide
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Peptides are biologically occurring short chains of amino acid monomers linked by peptide bonds. The covalent chemical bonds are formed when the group of one amino acid reacts with the amine group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a peptide bond, followed by tripeptides, tetrapeptides. A polypeptide is a long, continuous, and unbranched peptide chain, hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides and polysaccharides, etc. Peptides are distinguished from proteins on the basis of size, all peptides except cyclic peptides have an N-terminal and C-terminal residue at the end of the peptide. Ribosomal peptides Ribosomal peptides are synthesized by translation of mRNA and they are often subjected to proteolysis to generate the mature form. These function, typically in higher organisms, as hormones and signaling molecules, some organisms produce peptides as antibiotics, such as microcins. Since they are translated, the amino acid residues involved are restricted to those utilized by the ribosome, however, these peptides frequently have posttranslational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, they are linear, although lariat structures have been observed, more exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom. Nonribosomal peptides Nonribosomal peptides are assembled by enzymes that are specific to each peptide, the most common non-ribosomal peptide is glutathione, which is a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in organisms, plants. These complexes are often out in a similar fashion. These peptides are often cyclic and can have highly complex cyclic structures, since the system is closely related to the machinery for building fatty acids and polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion, Peptones See also Tryptone Peptones are derived from animal milk or meat digested by proteolysis. In addition to containing small peptides, the material includes fats, metals, salts, vitamins. Peptones are used in nutrient media for growing bacteria and fungi, Peptide fragments Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Peptides received prominence in molecular biology for several reasons, the first is that peptides allow the creation of peptide antibodies in animals without the need of purifying the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest and these will then be used to make antibodies in a rabbit or mouse against the protein
6.
Random coil
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A random coil is a polymer conformation where the monomer subunits are oriented randomly while still being bonded to adjacent units. It is not one specific shape, but a statistical distribution of shapes for all the chains in a population of macromolecules, the conformations name is derived from the idea that, in the absence of specific, stabilizing interactions, a polymer backbone will sample all possible conformations randomly. Many linear, unbranched homopolymers — in solution, or above their melting temperatures — assume random coils, even copolymers with monomers of unequal length will distribute in random coils if the subunits lack any specific interactions. The parts of branched polymers may also assume random coils, below their melting temperatures, most thermoplastic polymers have amorphous regions in which the chains approximate random coils, alternating with regions that are crystalline. The amorphous regions contribute elasticity and the crystalline regions contribute strength, more complex polymers such as proteins, with various interacting chemical groups attached to their backbones, self-assemble into well-defined structures. This is not actually the case, since the ensemble will be energy weighted due to interactions between amino acid side-chains, with lower-energy conformations being present more frequently, in addition, even arbitrary sequences of amino acids tend to exhibit some hydrogen bonding and secondary structure. For this reason, the term statistical coil is occasionally preferred, the conformational entropy associated with the random-coil state significantly contributes to its energetic stabilization and accounts for much of the energy barrier to protein folding. A random-coil conformation can be detected using spectroscopic techniques, the arrangement of the planar amide bonds results in a distinctive signal in circular dichroism. The chemical shift of amino acids in a conformation is well known in nuclear magnetic resonance. Deviations from these signatures often indicates the presence of secondary structure. Furthermore, there are signals in multidimensional NMR experiments that indicate that stable, likewise, in the images produced by crystallography experiments, segments of random coil result simply in a reduction in electron density or contrast. A randomly coiled state for any polypeptide chain can be attained by denaturing the system, however, there is evidence that proteins are never truly random coils, even when denatured. So, if each conformation has a probability or statistical weight. In an ensemble of chains, most of them will, therefore and this is the kind of shape any one of them will have most of the time. Consider a linear polymer to be a chain with N subunits, each of length ℓ. One can regard the segments of such chain in an ensemble as performing a random walk in three dimensions, limited only by the constraint that each segment must be joined to its neighbors. This is the ideal chain mathematical model and it is clear that the maximum, fully extended length L of the chain is N × ℓ.5. Note that although this model is termed a Gaussian chain, the function is not a gaussian distribution
7.
Translation (biology)
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In molecular biology and genetics, translation is the process in which ribosomes in a cells cytoplasm create proteins, following transcription of DNA to RNA in the cells nucleus. The entire process is a part of gene expression, in translation, messenger RNA is decoded by a ribosome, outside the nucleus, to produce a specific amino acid chain, or polypeptide. The polypeptide later folds into a protein and performs its functions in the cell. The ribosome facilitates decoding by inducing the binding of complementary tRNA anticodon sequences to mRNA codons, the tRNAs carry specific amino acids that are chained together into a polypeptide as the mRNA passes through and is read by the ribosome. Translation proceeds in three phases, Initiation, The ribosome assembles around the target mRNA, the first tRNA is attached at the start codon. Elongation, The tRNA transfers an amino acid to the corresponding to the next codon. The ribosome then moves to the next mRNA codon to continue the process, termination, When a stop codon is reached, the ribosome releases the polypeptide. In bacteria, translation occurs in the cytoplasm, where the large, in eukaryotes, translation occurs in the cytosol or across the membrane of the endoplasmic reticulum in a process called vectorial synthesis. Many types of transcribed RNA, such as transfer RNA, ribosomal RNA, a number of antibiotics act by inhibiting translation. These include anisomycin, cycloheximide, chloramphenicol, tetracycline, streptomycin, erythromycin, prokaryotic ribosomes have a different structure from that of eukaryotic ribosomes, and thus antibiotics can specifically target bacterial infections without any harm to a eukaryotic hosts cells. The basic process of production is addition of one amino acid at a time to the end of a protein. This operation is performed by a ribosome, a ribosome is made up of two subunits, a small subunit and a large subunit. These subunits come together before translation of mRNA into a protein to provide a location for translation to be carried out, the choice of amino acid type to add is determined by an mRNA molecule. Each amino acid added is matched to a three nucleotide subsequence of the mRNA, for each such triplet possible, the corresponding amino acid is accepted. The successive amino acids added to the chain are matched to successive nucleotide triplets in the mRNA, in this way the sequence of nucleotides in the template mRNA chain determines the sequence of amino acids in the generated amino acid chain. Addition of an amino acid occurs at the C-terminus of the peptide, the mRNA carries genetic information encoded as a ribonucleotide sequence from the chromosomes to the ribosomes. The ribonucleotides are read by translational machinery in a sequence of nucleotide triplets called codons, each of those triplets codes for a specific amino acid. The ribosome molecules translate this code to a sequence of amino acids
8.
Messenger RNA
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Messenger RNA is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression. As in DNA, mRNA genetic information is in the sequence of nucleotides, each codon encodes for a specific amino acid, except the stop codons, which terminate protein synthesis. It should not be confused with mitochondrial DNA, the brief existence of an mRNA molecule begins with transcription, and ultimately ends in degradation. During its life, a molecule may also be processed, edited. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic mRNA molecules do not, a molecule of eukaryotic mRNA and the proteins surrounding it are together called a messenger RNP. Transcription is when RNA is made from DNA, during transcription, RNA polymerase makes a copy of a gene from the DNA to mRNA as needed. This process is similar in eukaryotes and prokaryotes, the short-lived, unprocessed or partially processed product is termed precursor mRNA, or pre-mRNA, once completely processed, it is termed mature mRNA. Processing of mRNA differs greatly among eukaryotes, bacteria, and archea, non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires extensive processing, a 5 cap is a modified guanine nucleotide that has been added to the front or 5 end of a eukaryotic messenger RNA shortly after the start of transcription. The 5 cap consists of a terminal 7-methylguanosine residue that is linked through a 5-5-triphosphate bond to the first transcribed nucleotide and its presence is critical for recognition by the ribosome and protection from RNases. Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other, shortly after the start of transcription, the 5 end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the reactions that are required for mRNA capping. Synthesis proceeds as a biochemical reaction. In some instances, an mRNA will be edited, changing the composition of that mRNA. An example in humans is the apolipoprotein B mRNA, which is edited in some tissues, the editing creates an early stop codon, which, upon translation, produces a shorter protein. Polyadenylation is the covalent linkage of a moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA molecules are polyadenylated at the 3 end, the poly tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, MRNA can also be polyadenylated in prokaryotic organisms, where poly tails act to facilitate, rather than impede, exonucleolytic degradation
9.
Amino acid
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Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an acid are carbon, hydrogen, oxygen. About 500 amino acids are known and can be classified in many ways, in the form of proteins, amino acids comprise the second-largest component of human muscles, cells and other tissues. Outside proteins, amino acids perform critical roles in such as neurotransmitter transport. In biochemistry, amino acids having both the amine and the acid groups attached to the first carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids and they include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins. These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as standard amino acids. The other two are selenocysteine, and pyrrolysine, pyrrolysine and selenocysteine are encoded via variant codons, for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine is generally considered as a form of methionine rather than as a separate proteinogenic amino acid, codon–tRNA combinations not found in nature can also be used to expand the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids also play critical roles within the body. Nine proteinogenic amino acids are called essential for humans because they cannot be created from other compounds by the human body, others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species, because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production of drugs, biodegradable plastics, the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. Glycine and leucine were discovered in 1820, usage of the term amino acid in the English language is from 1898. Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis, in the structure shown at the top of the page, R represents a side chain specific to each amino acid. The carbon atom next to the group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as amino acids
10.
Ribosome
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The ribosome is a complex molecular machine, found within all living cells, that serves as the site of biological protein synthesis. Ribosomes link amino acids together in the order specified by messenger RNA molecules, ribosomes consist of two major components, the small ribosomal subunit, which reads the RNA, and the large subunit, which joins amino acids to form a polypeptide chain. Each subunit is composed of one or more ribosomal RNA molecules, the ribosomes and associated molecules are also known as the translational apparatus. The sequence of DNA, which encodes the sequence of the acids in a protein, is copied into a messenger RNA chain. It may be copied many times into RNA chains, ribosomes can bind to a messenger RNA chain and use its sequence for determining the correct sequence of amino acids. Amino acids are selected, collected, and carried to the ribosome by transfer RNA molecules and it is during this binding that the correct translation of nucleic acid sequence to amino acid sequence occurs. For each coding triplet in the messenger RNA there is a distinct transfer RNA that matches, the attached amino acids are then linked together by another part of the ribosome. Once the protein is produced, it can then fold to produce a specific functional three-dimensional structure although during synthesis some proteins start folding into their correct form, a ribosome is made from complexes of RNAs and proteins and is therefore a ribonucleoprotein. When a ribosome finishes reading an mRNA molecule, these two subunits split apart, ribosomes are ribozymes, because the catalytic peptidyl transferase activity that links amino acids together is performed by the ribosomal RNA. Ribosomes are often associated with the membranes that make up the rough endoplasmic reticulum. Ribosomes from bacteria, archaea and eukaryotes in the system, resemble each other to a remarkable degree. They differ in their size, sequence, structure, and the ratio of protein to RNA, the differences in structure allow some antibiotics to kill bacteria by inhibiting their ribosomes, while leaving human ribosomes unaffected. In bacteria and archaea, more than one ribosome may move along a single mRNA chain at one time, each reading its sequence, ribosomes were first observed in the mid-1950s by Romanian cell biologist George Emil Palade, using an electron microscope, as dense particles or granules. The Nobel Prize in Chemistry 2009 was awarded to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for determining the detailed structure, the ribosome is a highly complex cellular machine. It is largely made up of specialized RNA known as ribosomal RNA as well as dozens of distinct proteins, the ribosomal proteins and rRNAs are arranged into two distinct ribosomal pieces of different size, known generally as the large and small subunit of the ribosome. Ribosomes consist of two subunits that fit together and work as one to translate the mRNA into a polypeptide chain during protein synthesis, because they are formed from two subunits of non-equal size, they are slightly longer in the axis than in diameter. Prokaryotic ribosomes are around 20 nm in diameter and are composed of 65% rRNA, eukaryotic ribosomes are between 25 and 30 nm in diameter with an rRNA-to-protein ratio that is close to 1. Bacterial ribosomes are composed of one or two rRNA strands, eukaryotic ribosomes contain one or three very large rRNA molecules and multiple smaller protein molecules
11.
Anfinsen's dogma
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Anfinsens dogma is a postulate in molecular biology that, at least for small globular proteins, the native structure is determined only by the proteins amino acid sequence. The dogma was championed by the Nobel Prize Laureate Christian B, Anfinsen from his research on the folding of ribonuclease A. The postulate amounts to saying that, at the conditions at which folding occurs. The three conditions, Uniqueness, requires that the sequence does not have any other configuration with a free energy. Hence the free energy minimum must be unchallenged, stability, small changes in the surrounding environment cannot give rise to changes in the minimum configuration. How the protein reaches this structure is the subject of the field of protein folding, also, some proteins need the assistance of another protein called a chaperone protein to fold properly. It has been suggested that this disproves Anfinsens dogma, however, the chaperones do not appear to affect the final state of the protein, they seem to work primarily by preventing aggregation of several protein molecules before the protein is folded. Prions are an exception to Anfinsens dogma, prions are stable conformations of proteins which differ from the native folding state. In Bovine spongiform encephalopathy, native proteins re-fold into a different stable conformation, other amyloid diseases, including Alzheimers disease and Parkinsons disease, are also exceptions to Anfinsens dogma. Sela M, White FH Jr, Anfinsen CB, reductive cleavage of disulfide bridges in ribonuclease. Studies on the reduction and re-formation of protein disulfide bonds, chemical structures of pancreatic ribonuclease and deoxyribonuclease. Profiles in Science, The Christian B
12.
Intrinsically disordered proteins
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An intrinsically disordered protein is a protein that lacks a fixed or ordered three-dimensional structure. IDPs cover a spectrum of states from fully unstructured to partially structured and include random coils, molten globules and they constitute one of the main types of protein. The discovery of IDPs has challenged the traditional protein structure paradigm and this dogma has been challenged over the last decades by increasing evidence from various branches of structural biology, suggesting that protein dynamics may be highly relevant for such systems. Despite their lack of structure, IDPs are a very large. In some cases, IDPs can adopt a fixed three-dimensional structure after binding to other macromolecules, overall, IDPs are different from structured proteins in many ways and tend to have distinct properties in terms of function, structure, sequence, interactions, evolution and regulation. In the 1930s -1950s, the first protein structures were solved by protein crystallography and these early structures suggested that a fixed three-dimensional structure might be generally required to mediate biological functions of proteins. When stating that proteins have just one uniquely defined configuration, Mirsky and Pauling did not recognize that Fishers work would have supported their thesis with his Lock and Key model. These publications solidified the central dogma of biology in that the sequence determines the structure which, in turn. In 1950, Karush wrote about Configurational Adaptability contradicting all the assumptions and he was convinced that proteins have more than one configuration at the same energy level and can choose one when binding to other substrates. In the 1960s, Levinthals paradox suggested that the systematic search of a long polypeptide is unlikely to yield a single folded protein structure on biologically relevant timescales. Curiously, for proteins or protein domains, relatively rapid. During the subsequent decades, however, many large protein regions could not be assigned in x-ray datasets, indicating that they occupy multiple positions, the lack of fixed, unique positions relative to the crystal lattice suggested that these regions were disordered. Nuclear magnetic resonance spectroscopy of proteins also demonstrated the presence of large flexible linkers, based on DISOPRED2 prediction, long disordered segments occur in 2. 0% of archaean,4. 2% of eubacterial and 33. 0% of eukaryotic proteins. In 2001, Dunker published his paper Intrinsically Disordered Proteins questioning whether the newly found information was ignored for 50 years, in the 2010s it became clear that IDPs are highly abundant among disease-related proteins. Intrinsic disorder is particularly enriched in proteins implicated in signaling, transcription. Disordered regions are found as flexible linkers or loops connecting domains. Linker sequences vary greatly in length but are rich in polar uncharged amino acids. Flexible linkers allow the connecting domains to freely twist and rotate to recruit their binding partners via protein domain dynamics, many roles of linear motifs are associated with cell regulation, for instance in control of cell shape, subcellular localisation of individual proteins and regulated protein turnover
13.
Protein dynamics
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Proteins are generally thought to adopt unique structures determined by their amino acid sequences, as outlined by Anfinsens dogma. However, proteins are not strictly static objects, but rather populate ensembles of conformations, transitions between these states occur on a variety of length scales and time scales, and have been linked to functionally relevant phenomena such as allosteric signaling and enzyme catalysis. The study of dynamics is most directly concerned with the transitions between these states, but can also involve the nature and equilibrium populations of the states themselves. Portions of protein structures often deviate from the equilibrium state, some such excursions are harmonic, such as stochastic fluctuations of chemical bonds and bond angles. Others are anharmonic, such as sidechains that jump between separate discrete energy minima, or rotamers, evidence for local flexibility is often obtained from NMR spectroscopy. Flexible and potentially disordered regions of a protein can be detected using the random coil index, flexibility in folded proteins can be identified by analyzing the spin relaxation of individual atoms in the protein. Many residues are in spatial proximity in protein structures. This is true for most residues that are contiguous in the primary sequence, because of this proximity, these residuess energy landscapes become coupled based on various biophysical phenomena such as hydrogen bonds, ionic bonds, and van der Waals interactions. Transitions between states for such sets of residues therefore become correlated and this is perhaps most obvious for surface-exposed loops, which often shift collectively to adopt different conformations in different crystal structures. However, coupled conformational heterogeneity is also evident in secondary structure. For example, consecutive residues and residues offset by 4 in the sequence often interact in α helices. When these coupled residues form pathways linking functionally important parts of a protein, the presence of multiple domains in proteins gives rise to a great deal of flexibility and mobility, leading to protein domain dynamics. Domain motions can be inferred by comparing different structures of a protein and they can also be suggested by sampling in extensive molecular dynamics trajectories and principal component analysis. The phosphoinositide domain swivels between two states in order to bring a group from the active site of the nucleotide binding domain to that of the phosphoenolpyruvate/pyruvate domain. The phosphate group is moved over a distance of 45 Å involving a domain motion of about 100 degrees around a single residue. In enzymes, the closure of one domain onto another captures a substrate by an induced fit, a detailed analysis by Gerstein led to the classification of two basic types of domain motion, hinge and shear. Only a relatively small portion of the chain, namely the inter-domain linker, a study by Hayward found that the termini of α-helices and β-sheets form hinges in a large number of cases. Many hinges were found to two secondary structure elements acting like hinges of a door, allowing an opening and closing motion to occur
14.
Disease
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A disease is a particular abnormal condition, a disorder of a structure or function, that affects part or all of an organism. The study of disease is called pathology which includes the study of cause, Disease is often construed as a medical condition associated with specific symptoms and signs. When caused by pathogens, even in the literature, the term disease is often misleadingly used in the place of its causal agent. This language habitat can cause confusion in the communication of the principle in epidemiology. Diseases can affect not only physically, but also emotionally. Death due to disease is called death by natural causes, there are four main types of disease, infectious diseases, deficiency diseases, genetic diseases, and physiological diseases. Diseases can also be classified as communicable and non-communicable, the deadliest diseases in humans are coronary artery disease, followed by cerebrovascular disease and lower respiratory infections. In many cases, terms such as disease, disorder, morbidity, there are situations, however, when specific terms are considered preferable. Disease The term disease broadly refers to any condition that impairs the normal functioning of the body, for this reason, diseases are associated with dysfunctioning of the bodys normal homeostatic processes. The term disease has both a count sense and a noncount sense, by contrast, an infection that is asymptomatic during its incubation period, but expected to produce symptoms later, is usually considered a disease. Non-infectious diseases are all other diseases, including most forms of cancer, heart disease, acquired disease disease that began at some point during ones lifetime, as opposed to disease that was already present at birth, which is congenital disease. Acquired sounds like it could mean caught via contagion, but it simply means acquired sometime after birth and it also sounds like it could imply secondary disease, but acquired disease can be primary disease. It is often, genetic and can be inherited and it can also be the result of a vertically transmitted infection from the mother such as HIV/AIDS. Genetic disease disease that is caused by genetic mutation and it is often inherited, but some mutations are random and de novo. Hereditary or inherited disease a type of disease caused by mutation that is hereditary Iatrogenic disease A disease condition caused by medical intervention. Idiopathic disease disease whose cause is unknown, as medical science has advanced, many diseases whose causes were formerly complete mysteries have been somewhat explained or even extensively explained. Bacterial infections can be primary or secondary to a viral infection or burn. Terminal disease disease with death as an inevitable result Illness Illness is generally used as a synonym for disease, however, this term is occasionally used to refer specifically to the patients personal experience of his or her disease
15.
Amyloid
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Amyloids are aggregates of proteins that become folded into a shape that allows many copies of that protein to stick together forming fibrils. Such amyloids have been associated more than 20 human diseases, known as amyloidosis. Some amyloid proteins are infectious, these are called prions in which the form can act as a template to convert other non-infectious proteins into infectious form. Amyloids have been known to arise from different proteins and polypeptides. These polypeptide chains generally form β-sheet structures that aggregate into long fibers, however, the diversity of the conformations may have led to different forms of the prion diseases. The name amyloid comes from the mistaken identification by Rudolf Virchow of the substance as starch. The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting beta sheet structure, common to most cross-beta-type structures, in general, they are identified by apple-green birefringence when stained with congo red and seen under polarized light. These deposits often recruit various sugars and other such as Serum Amyloid P component, resulting in complex. Recently this definition has come into question as some classic, amyloid species have been observed in distinctly intracellular locations, a more recent, biophysical definition is broader, including any polypeptide that polymerizes to form a cross-beta structure, in vivo or in vitro. Some of these, although demonstrably cross-beta sheet, do not show some classic histopathological characteristics such as the Congo-red birefringence, microbiologists and biophysicists have largely adopted this definition, leading to some conflict in the biological community over an issue of language. The remainder of this article use the biophysical context. The International Society of Amyloidosis classifies amyloid fibrils based upon associated proteins, native amyloids in organismsCurli fibrils produced by E. coli, Salmonella, and a few other members of the Enterobacteriales. The genetic elements encoding the curli system are phylogenetic widespread and can be found in at least four bacterial phyla and this suggest that many more bacteria may express curli fibrils. g. The major component of amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or amylin. This is stored with insulin in secretory granules in B cells and is co secreted with insulin, each individual fiber may be 5–15 nanometres in width and a few micrometres in length. The term cross-beta was based on the observation of two sets of lines, one longitudinal and one transverse, that form a characteristic cross pattern. There are two characteristic scattering diffraction signals produced at 4.7 and 10 Ångstroms, corresponding to the interstrand, the stacks of beta sheet are short and traverse the breadth of the amyloid fibril, the length of the amyloid fibril is built by aligned strands. The cross-beta pattern is considered a hallmark of amyloid structure
16.
Immune system
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The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, a system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms. In many species, the system can be classified into subsystems, such as the innate immune system versus the adaptive immune system. In humans, the barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system. Even simple unicellular organisms such as bacteria possess a rudimentary immune system in the form of enzymes that protect against bacteriophage infections, other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants and invertebrates. These mechanisms include phagocytosis, antimicrobial peptides called defensins, and the complement system, jawed vertebrates, including humans, have even more sophisticated defense mechanisms, including the ability to adapt over time to recognize specific pathogens more efficiently. Adaptive immunity creates immunological memory after a response to a specific pathogen. This process of acquired immunity is the basis of vaccination, disorders of the immune system can result in autoimmune diseases, inflammatory diseases and cancer. Immunodeficiency occurs when the system is less active than normal. In humans, immunodeficiency can either be the result of a disease such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS. In contrast, autoimmunity results from an immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimotos thyroiditis, rheumatoid arthritis, diabetes mellitus type 1, immunology covers the study of all aspects of the immune system. Immunology is a science that examines the structure and function of the immune system and it originates from medicine and early studies on the causes of immunity to disease. The earliest known reference to immunity was during the plague of Athens in 430 BC, thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. In the 18th century, Pierre-Louis Moreau de Maupertuis made experiments with scorpion venom and observed that certain dogs and this and other observations of acquired immunity were later exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of disease. Pasteurs theory was in opposition to contemporary theories of disease. It was not until Robert Kochs 1891 proofs, for which he was awarded a Nobel Prize in 1905, viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed. Immunology made an advance towards the end of the 19th century, through rapid developments, in the study of humoral immunity
17.
Antibody
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An antibody, also known as an immunoglobulin, is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as bacteria and viruses. The antibody recognizes a molecule of the harmful agent, called an antigen. Each tip of the Y of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or a cell for attack by other parts of the immune system. Depending on the antigen, the binding may impede the process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the components of the immune system is mediated via its Fc region. The production of antibodies is the function of the humoral immune system. Antibodies are secreted by B cells of the immune system. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, therefore, soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms. Antibodies are glycoproteins belonging to the immunoglobulin superfamily and they constitute most of the gamma globulin fraction of the blood proteins. They are typically made of basic structural units—each with two heavy chains and two small light chains. There are several different types of heavy chains that define the five different types of crystallisable fragments that may be attached to the antigen-binding fragments. The five different types of Fc regions allow antibodies to be grouped into five isotypes, each Fc region of a particular antibody isotype is able to bind to its specific Fc Receptor, thus allowing the antigen-antibody complex to mediate different roles depending on which FcR it binds. The ability of an antibody to bind to its corresponding FcR is further modulated by the structure of the present at conserved sites within its Fc region. The ability of antibodies to bind to FcRs helps to direct the immune response for each different type of foreign object they encounter. For example, IgE is responsible for an allergic response consisting of mast cell degranulation, igEs Fab paratope binds to allergic antigen, for example house dust mite particles, while its Fc region binds to Fc receptor ε. The allergen-IgE-FcRε interaction mediates allergic signal transduction to induce conditions such as asthma and this region is known as the hypervariable region. Each of these variants can bind to a different antigen and this enormous diversity of antibody paratopes on the antigen-binding fragments allows the immune system to recognize an equally wide variety of antigens
18.
Denaturation (biochemistry)
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If proteins in a living cell are denatured, this results in disruption of cell activity and possibly cell death. Protein denaturation is also a consequence of cell death, denatured proteins can exhibit a wide range of characteristics, from conformational change and loss of solubility to aggregation due to the exposure of hydrophobic groups. Protein folding is key to whether a protein or a membrane protein can do its job correctly. It must be folded into the shape to function. This is one reason why tight homeostasis is physiologically necessary in life forms. This concept is unrelated to denatured alcohol, which is alcohol that has mixed with additives to make it unsuitable for human consumption. When food is cooked, some of its proteins become denatured and this is why boiled eggs become hard and cooked meat becomes firm. A classic example of denaturing in proteins comes from egg whites, fresh from the eggs, egg whites are transparent and liquid. Cooking the thermally unstable whites turns them opaque, forming a solid mass. The same transformation can be effected with a denaturing chemical, pouring egg whites into a beaker of acetone will also turn egg whites translucent and solid. The skin that forms on curdled milk is another example of denatured protein. The cold appetizer known as ceviche is prepared by cooking raw fish and shellfish in an acidic citrus marinade. Denatured proteins can exhibit a range of characteristics, from loss of solubility to protein aggregation. The newly created protein strand then undergoes posttranslational modification, in which additional atoms or molecules are added, for copper, zinc. The final shape of a protein determines how it interacts with its environment, when a protein is denatured, secondary and tertiary structures are altered but the peptide bonds of the primary structure between the amino acids are left intact. Since all structural levels of the protein determine its function, the protein can no longer perform its function once it has been denatured and this is in contrast to intrinsically unstructured proteins, which are unfolded in their native state, but still functionally active. In quaternary structure denaturation, protein sub-units are dissociated and/or the spatial arrangement of protein subunits is disrupted, in secondary structure denaturation, proteins lose all regular repeating patterns such as alpha-helices and beta-pleated sheets, and adopt a random coil configuration. Primary structure, such as the sequence of amino acids held together by covalent peptide bonds, is not disrupted by denaturation, most biological substrates lose their biological function when denatured
19.
Protein primary structure
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Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the structure of a protein is reported starting from the amino-terminal end to the carboxyl-terminal end. Protein biosynthesis is most commonly performed by ribosomes in cells, peptides can also be synthesised in the laboratory. Protein primary structures can be sequenced, or inferred from DNA sequences. Amino acids are polymerised via peptide bonds to form a long backbone, in biological systems, proteins are produced during translation by a cells ribosomes. Some organisms can also make short peptides by non-ribosomal peptide synthesis, which often use amino acids other than the standard 20, peptides can be synthesised chemically via a range of laboratory methods. Chemical methods typically synthesise peptides in the order to biological protein synthesis. Protein sequence is typically notated as a string of letters, listing the amino acids starting at the end through to the carboxyl-terminal end. Either a three letter code or single letter code can be used to represent the 20 naturally occurring amino acids, peptides can be directly sequenced, or inferred from DNA sequences. Large sequence databases now exist that collate known protein sequences, in general, polypeptides are unbranched polymers, so their primary structure can often be specified by the sequence of amino acids along their backbone. The chiral centers of a chain can undergo racemization. Although it does not change the sequence, it affect the chemical properties of the sequence. In particular, the L-amino acids normally found in proteins can spontaneously isomerize at the C α atom to form D-amino acids, additionally, proline can form stable trans-isomers at the peptide bond. Finally, the protein can undergo a variety of posttranslational modifications, formylation − C H The N-terminal methionine usually found after translation has an N-terminus blocked with a formyl group. This formyl group is removed by the enzyme deformylase, pyroglutamate An N-terminal glutamine can attack itself, forming a cyclic pyroglutamate group. Myristoylation − C −12 − C H3 Similar to acetylation, instead of a simple methyl group, the myristoyl group has a tail of 14 hydrophobic carbons, which make it ideal for anchoring proteins to cellular membranes. The C-terminal carboxylate group of a polypeptide can also be modified, Glycosyl phosphatidylinositol attachment Glycosyl phosphatidylinositol is a large, hydrophobic phospholipid prosthetic group that achors proteins to cellular membranes. It is attached to the polypeptide C-terminus through a linkage that then connects to ethanolamine, thence to sundry sugars
20.
Protein secondary structure
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Protein secondary structure is the three dimensional form of local segments of proteins. The two most common structural elements are alpha helices and beta sheets. Secondary structure elements typically spontaneously form as an intermediate before the protein folds into its three dimensional tertiary structure, Secondary structure is formally defined by the pattern of hydrogen bonds between the amine hydrogen and carbonyl oxygen atoms in the peptide backbone. The concept of structure was first introduced by Kaj Ulrik Linderstrøm-Lang at Stanford in 1952. Other types of such as nucleic acids also possess characteristic secondary structures. The most common structures are alpha helices and beta sheets. Other extended structures such as the helix and alpha sheet are rare in native state proteins but are often hypothesized as important protein folding intermediates. Tight turns and loose, flexible loops link the more regular secondary structure elements, the random coil is not a true secondary structure, but is the class of conformations that indicate an absence of regular secondary structure. Amino acids vary in their ability to form the secondary structure elements. However, these preferences are not strong enough to produce a method of predicting secondary structure from sequence alone. Low frequency collective vibrations are thought to be sensitive to local rigidity within proteins, neutron scattering measurements have directly connected the spectral feature at ~1 THz to collective motions of the secondary structure of beta-barrel protein GFP. Hydrogen bonding patterns in secondary structures may be distorted, which makes an automatic determination of secondary structure difficult. There are several methods for formally defining protein secondary structure, the Dictionary of Protein Secondary Structure, in short DSSP, is commonly used to describe the protein secondary structure with single letter codes. The secondary structure is assigned based on hydrogen bonding patterns as those proposed by Pauling et al. in 1951. There are eight types of structure that DSSP defines, G = 3-turn helix. T = hydrogen bonded turn E = extended strand in parallel and/or anti-parallel β-sheet conformation, B = residue in isolated β-bridge S = bend. Coil is often codified as, C or -, the helices and sheet conformations are all required to have a reasonable length. This means that 2 adjacent residues in the structure must form the same hydrogen bonding pattern
21.
Alpha helix
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This secondary structure is also sometimes called a classic Pauling–Corey–Branson α-helix. The name 3. 613-helix is also used for type of helix, denoting the average number of residues per helical turn. Among types of structure in proteins, the α-helix is the most regular. In the early 1930s, William Astbury showed that there were changes in the X-ray fiber diffraction of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a molecular structure with a characteristic repeat of ~5.1 ångströms. Astbury initially proposed a structure for the fibers. He later joined other researchers in proposing that, the protein molecules formed a helix the stretching caused the helix to uncoil. Hans Neurath was the first to show that Astburys models could not be correct in detail, neuraths paper and Astburys data inspired H. S. Taylor, Maurice Huggins and Bragg and collaborators to propose models of keratin that somewhat resemble the modern α-helix. The pivotal moment came in the spring of 1948, when Pauling caught a cold. Being bored, he drew a polypeptide chain of roughly correct dimensions on a strip of paper and folded it into a helix, after a few attempts, he produced a model with physically plausible hydrogen bonds. Pauling then worked with Corey and Branson to confirm his model before publication. The amino acids in an α-helix are arranged in a helical structure where each amino acid residue corresponds to a 100° turn in the helix. Dunitz describes how Paulings first article on the theme in fact shows a left-handed helix, short pieces of left-handed helix sometimes occur with a large content of achiral glycine amino acids, but are unfavorable for the other normal, biological L-amino acids. The pitch of the alpha-helix is 5.4 Å, which is the product of 1.5 and 3.6, the alpha-helices can be identified in protein structure using several computational methods, one of which being DSSP. Similar structures include the 310 helix and the π-helix, the subscripts refer to the number of atoms in the closed loop formed by the hydrogen bond. Residues in α-helices typically adopt backbone dihedral angles around, as shown in the image at right, in more general terms, they adopt dihedral angles such that the ψ dihedral angle of one residue and the φ dihedral angle of the next residue sum to roughly -105°. As a consequence, α-helical dihedral angles, in general, fall on a stripe on the Ramachandran diagram. For comparison, the sum of the angles for a 310 helix is roughly -75°
22.
Beta sheet
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The β-sheet is a common motif of regular secondary structure in proteins. Beta sheets consist of beta strands connected laterally by at least two or three hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation, the supramolecular association of β-sheets has been implicated in formation of the protein aggregates and fibrils observed in many human diseases, notably the amyloidoses such as Alzheimers disease. The first β-sheet structure was proposed by William Astbury in the 1930s and he proposed the idea of hydrogen bonding between the peptide bonds of parallel or antiparallel extended β-strands. However, Astbury did not have the data on the bond geometry of the amino acids in order to build accurate models. A refined version was proposed by Linus Pauling and Robert Corey in 1951 and their model incorporated the planarity of the peptide bond which they previously explained as resulting from keto-enol tautomerization. In the fully extended β-strand, successive side chains point straight up, then straight down, then straight up, adjacent β-strands in a β-sheet are aligned so that their Cα atoms are adjacent and their side chains point in the same direction. 5°. The pleating causes the distance between C α i and C i +2 α to be approximately 6 Å, rather than the 7.6 Å expected from two fully extended trans peptides, the sideways distance between adjacent Cα atoms in hydrogen-bonded β-strands is roughly 5 Å. However, β-strands are rarely extended, rather, they exhibit a twist due to the chirality of their component amino acids. The energetically preferred dihedral angles near = diverge significantly from the extended conformation =. The twist is often associated with alternating fluctuations in the angles to prevent the individual β-strands in a larger sheet from splaying apart. A good example of a strongly twisted β-hairpin can be seen in the protein BPTI, the side chains point outwards from the folds of the pleats, roughly perpendicularly to the plane of the sheet, successive residues point outwards on alternating faces of the sheet. Because peptide chains have a directionality conferred by their N-terminus and C-terminus and they are usually represented in protein topology diagrams by an arrow pointing toward the C-terminus. Adjacent β-strands can form hydrogen bonds in antiparallel, parallel, or mixed arrangements, in an antiparallel arrangement, the successive β-strands alternate directions so that the N-terminus of one strand is adjacent to the C-terminus of the next. The peptide backbone dihedral angles are about in antiparallel sheets, the dihedral angles are about in parallel sheets. For example, residue i may form bonds to residues j −1 and j +1. By contrast, residue j may hydrogen-bond to different residues altogether, finally, an individual strand may exhibit a mixed bonding pattern, with a parallel strand on one side and an antiparallel strand on the other. Also proteins are inherently constrained by folding kinetics as well as folding thermodynamics, the hydrogen bonding of β-strands need not be perfect, but can exhibit localized disruptions known as β-bulges
23.
Intramolecular force
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Intramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule, a property or phenomenon limited to the extent of a single molecule. Intramolecular hydride transfer intramolecular hydrogen bond In intramolecular organic reactions, two sites are contained within a single molecule. This creates a high effective concentration, and, therefore. Examples of intramolecular reactions are the Smiles rearrangement, the Dieckmann condensation, tethered Intramolecular reactions entail the formation of four-membered rings from two functional groups in the same molecule, each functional group contributes two atoms. The length of the effects the stereochemical outcome of the reaction. Longer tethers tend to generate the product where the terminal carbon of the alkene is linked to the α-carbon of the enone. When the tether consists only two carbons, the product is generated where the β-carbon of the enone is connected to the terminal carbon of the alkene. Tethered reactions have been used to synthesize organic compounds with interesting ring systems, for example, photocyclization was used to construct the tricyclic core structure in Ginkgolide B by E. J. Corey and co-workers in 1988. Popular choices of tether contain a carbonate ester, boronic ester, silyl ether, the main hurdle for this strategy to work is selecting the proper length for the tether and making sure reactive groups have an optimal orientation with respect to each other. No reaction takes place when these groups are replaced by smaller methyl groups. Another example is a cycloaddition with two alkene groups tethered through a silicon acetal group, which is subsequently cleaved by TBAF yielding the endo-diol. Without the tether, the exo isomer forms
24.
Hydrogen bond
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Hydrogen bonds can occur between molecules or within different parts of a single molecule. Depending on geometry and environment, the hydrogen bond free energy content is between 1 and 5 kcal/mol and this makes it stronger than a van der Waals interaction, but weaker than covalent or ionic bonds. This type of bond can occur in molecules such as water and in organic molecules like DNA. Intermolecular hydrogen bonding is responsible for the boiling point of water compared to the other group 16 hydrides that have much weaker hydrogen bonds. Intramolecular hydrogen bonding is responsible for the secondary and tertiary structures of proteins. It also plays an important role in the structure of polymers, in 2011, an IUPAC Task Group recommended a modern evidence-based definition of hydrogen bonding, which was published in the IUPAC journal Pure and Applied Chemistry. An accompanying detailed technical report provides the rationale behind the new definition, a hydrogen atom attached to a relatively electronegative atom will play the role of the hydrogen bond donor. This electronegative atom is usually fluorine, oxygen, or nitrogen, a hydrogen attached to carbon can also participate in hydrogen bonding when the carbon atom is bound to electronegative atoms, as is the case in chloroform, CHCl3. An example of a hydrogen donor is the hydrogen from the hydroxyl group of ethanol. In a hydrogen bond, the electronegative atom not covalently attached to the hydrogen is named proton acceptor, because of the small size of hydrogen relative to other atoms and molecules, the resulting charge, though only partial, represents a large charge density. A hydrogen bond results when this positive charge density attracts a lone pair of electrons on another heteroatom. The hydrogen bond is described as an electrostatic dipole-dipole interaction. These covalent features are more substantial when acceptors bind hydrogens from more electronegative donors, the partially covalent nature of a hydrogen bond raises the following questions, To which molecule or atom does the hydrogen nucleus belong. And Which should be labeled donor and which acceptor, liquids that display hydrogen bonding are called associated liquids. Hydrogen bonds can vary in strength from weak to extremely strong. For example, the central interresidue N−H···N hydrogen bond between guanine and cytosine is much stronger in comparison to the N−H···N bond between the adenine-thymine pair, the length of hydrogen bonds depends on bond strength, temperature, and pressure. The bond strength itself is dependent on temperature, pressure, bond angle, the typical length of a hydrogen bond in water is 197 pm. The ideal bond angle depends on the nature of the hydrogen bond donor, moore and Winmill used the hydrogen bond to account for the fact that trimethylammonium hydroxide is a weaker base than tetramethylammonium hydroxide
25.
Linus Pauling
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Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He published more than 1,200 papers and books, of which about 850 dealt with scientific topics, new Scientist called him one of the 20 greatest scientists of all time, and as of 2000, he was rated the 16th most important scientist in history. Pauling was one of the founders of the fields of quantum chemistry, for his scientific work, Pauling was awarded the Nobel Prize in Chemistry in 1954. In 1962, for his activism, he was awarded the Nobel Peace Prize. This makes him the person to be awarded two unshared Nobel Prizes. He is one of four individuals to have won more than one Nobel Prize. Pauling is also one of two people to be awarded Nobel Prizes in different fields, the other being Marie Curie. Pauling also worked on DNAs structure, a problem which was solved by James Watson, Francis Crick, Rosalind Franklin, in his later years he promoted nuclear disarmament, as well as orthomolecular medicine, megavitamin therapy, and dietary supplements. None of the latter have gained acceptance in the scientific community. Pauling was born in Portland, Oregon, the child of Herman Henry William Pauling. He was named Linus Carl, in honor of Lucys father, Linus, in 1902, after his sister Pauline was born, Paulings parents decided to move out of Portland, to find more affordable and spacious living quarters than their one-room apartment. Lucy stayed with her husbands parents in Lake Oswego until Herman brought the family to Salem, within a year of Luciles birth in 1904, Herman Pauling moved his family to Oswego, where he opened his own drugstore. He moved his family to Condon, Oregon in 1905, by 1906, Herman Pauling was suffering from recurrent abdominal pain. He died of an ulcer on June 11,1910, leaving Lucy to care for Linus, Lucile. Pauling attributes his interest in becoming a chemist to being amazed by experiments conducted by a friend, Lloyd A. Jeffress, in high school, Pauling conducted chemistry experiments by scavenging equipment and material from an abandoned steel plant. With an older friend, Lloyd Simon, Pauling set up Palmon Laboratories in Simons basement and they approached local dairies offering to perform butterfat samplings at cheap prices but dairymen were wary of trusting two boys with the task, and the business ended in failure. At age 15, the high school senior had enough credits to enter Oregon State University, lacking two American history courses required for his high school diploma, Pauling asked the school principal if he could take the courses concurrently during the spring semester. Denied, he left Washington High School in June without a diploma, the school awarded him a diploma 45 years later, after he had won two Nobel Prizes
26.
Peptide bond
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A peptide bond is a covalent chemical bond linking two consecutive amino acid monomers along a peptide or protein chain. When two amino acids form a dipeptide through a peptide bond it is called condensation, in condensation, two amino acids approach each other, with the acid moiety of one coming near the amino moiety of the other. One loses a hydrogen and oxygen from its group and the other loses a hydrogen from its amino group. This reaction produces a molecule of water and two amino acids joined by a peptide bond, the two joined amino acids are called a dipeptide. The formation of the peptide bond consumes energy, which, in living systems, is derived from ATP, polypeptides and proteins are chains of amino acids held together by peptide bonds. Living organisms employ enzymes to produce polypeptides, and ribosomes to produce proteins, peptides are synthesized by specific enzymes. For example, the tripeptide glutathione is synthesized in two steps from free amino acids, by two enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase, a peptide bond can be broken by hydrolysis. In the presence of water they will break down and release 8–16 kilojoule/mol of free energy, in living organisms, the process is catalyzed by enzymes known as peptidases or proteases. The wavelength of absorption for a bond is 190–230 nm. Significant delocalisation of the pair of electrons on the nitrogen atom gives the group a partial double bond character. The partial double bond renders the amide group planar, occurring in either the cis or trans isomers. In the unfolded state of proteins, the groups are free to isomerize. The trans form is preferred overwhelmingly in most peptide bonds, however, X-Pro peptide groups tend to have a roughly 3,1 ratio, presumably because the symmetry between the C α and C δ atoms of proline makes the cis and trans isomers nearly equal in energy. The dihedral angle associated with the group is denoted ω, ω =0 ∘ for the cis isomer. Amide groups can isomerize about the C-N bond between the cis and trans forms, albeit slowly, the transition states ω = ±90 ∘ requires that the partial double bond be broken, so that the activation energy is roughly 80 kilojoule/mol. Conformational protein folding is much faster than cis-trans isomerization. A nonnative isomer of some groups can disrupt the conformational folding significantly. However, not all groups have the same effect on folding
27.
Amphiphile
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Amphiphile is a term describing a chemical compound possessing both hydrophilic and lipophilic properties. Such a compound is called amphiphilic or amphipathic and this forms the basis for a number of areas of research in chemistry and biochemistry, notably that of lipid polymorphism. Organic compounds containing hydrophilic groups at both ends of a molecule are called bolaamphiphilic. Common amphiphilic substances are soaps, detergents and lipoproteins, the lipophilic group is typically a large hydrocarbon moiety, such as a long chain of the form CH3n, with n >4. The hydrophilic group falls into one of the categories, Charged groups Anionic. Examples, with the part of the molecule represented by an R, are, carboxylates, RCO2−, sulfates, RSO4−, sulfonates. Phosphates, The charged functionality in phospholipids, examples are alcohols with large R groups, such as diacyl glycerol, and oligoethyleneglycols with long alkyl chains. Often, amphiphilic species have several parts, several hydrophilic parts. Proteins and some block copolymers are such examples, amphiphilic compounds have lipophilic structures and hydrophilic polar functional groups. As a result of having both lipophilic and hydrophilic portions, some compounds may dissolve in water and to some extent in non-polar organic solvents. When placed in an immiscible biphasic system consisting of aqueous and organic solvents, the extent of the hydrophobic and hydrophilic portions determines the extent of partitioning. Phospholipids, a class of molecules, are the main components of biological membranes. The amphiphilic nature of these molecules defines the way in which they form membranes, there are several examples of molecules that present amphiphilic properties, Hydrocarbon based surfactants are an example group of amphiphilic compounds. Their polar region can be either ionic, or non-ionic, some typical members of this group are, sodium dodecyl sulfate, Benzalkonium chloride, Cocamidopropyl betaine and 1-octanol. Many biological compounds are amphiphilic, phospholipids, cholesterol, glycolipids, fatty acids, bile acids, saponins, local anaesthetics etc
28.
Aqueous solution
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An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending to the relevant chemical formula, for example, a solution of table salt, or sodium chloride, in water would be represented as Na+ + Cl−. The word aqueous means pertaining to, related to, similar to, as water is an excellent solvent and is also naturally abundant, it is a ubiquitous solvent in chemistry. Substances that are hydrophobic often do not dissolve well in water, an example of a hydrophilic substance is sodium chloride. Acids and bases are aqueous solutions, as part of their Arrhenius definitions, the ability of a substance to dissolve in water is determined by whether the substance can match or exceed the strong attractive forces that water molecules generate between themselves. If the substance lacks the ability to dissolve in water the molecules form a precipitate, reactions in aqueous solutions are usually metathesis reactions. Metathesis reactions are another term for double-displacement, that is, when a cation displaces to form a bond with the other anion. The cation bonded with the latter anion will dissociate and bond with the other anion, aqueous solutions that conduct electric current efficiently contain strong electrolytes, while ones that conduct poorly are considered to have weak electrolytes. Those strong electrolytes are substances that are ionized in water. Nonelectrolytes are substances that dissolve in water yet maintain their molecular integrity, examples include sugar, urea, glycerol, and methylsulfonylmethane. When writing the equations of reactions, it is essential to determine the precipitate. To determine the precipitate, one must consult a chart of solubility, soluble compounds are aqueous, while insoluble compounds are the precipitate. Remember that there may not always be a precipitate, when performing calculations regarding the reacting of one or more aqueous solutions, in general one must know the concentration, or molarity, of the aqueous solutions. Solution concentration is given in terms of the form of the prior to it dissolving. Metal ions in aqueous solution Solubility Dissociation Acid-base reaction theories Properties of water Zumdahl S.1997, 4th ed. Boston, Houghton Mifflin Company
29.
Protein tertiary structure
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Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain backbone with one or more protein secondary structures, amino acid side chains may interact and bond in a number of ways. The interactions and bonds of side chains within a particular protein determine its tertiary structure, the protein tertiary structure is defined by its atomic coordinates. These coordinates may refer either to a domain or to the entire tertiary structure. A number of structures may fold into a quaternary structure. The science of the structure of proteins has progressed from one of hypothesis to one of detailed definition. Wrinch demonstrated this with the Cyclol model, the first prediction of the structure of a globular protein, contemporary methods are able to determine, without prediction, tertiary structures to within 5 Å for small proteins and, under favorable conditions, confident secondary structure predictions. Globular proteins have a core of hydrophobic amino acid residues and a region of water-exposed, charged. This arrangement may stabilise interactions within the tertiary structure, for example, in secreted proteins, which are not bathed in cytoplasm, disulfide bonds between cysteine residues help to maintain the tertiary structure. There is a commonality of stable tertiary structures seen in proteins of diverse function, for example, the TIM barrel, named for the enzyme triosephosphateisomerase, is a common tertiary structure as is the highly stable, dimeric, coiled coil structure. Hence, proteins may be classified by the structures they hold, databases of proteins which use such a classification include SCOP and CATH. The native state or native conformation of a protein is its most typical conformation in a cellular environment, protein chaperones within the cytoplasm of a cell assist a newly synthesised polypeptide to attain its native state. Folding kinetics may trap a protein in a high-energy conformation, the high-energy conformation may contribute to the function of the protein. For example, the influenza hemagglutinin protein is a polypeptide chain which when activated, is proteolytically cleaved to form two polypeptide chains. The two chains are held in a high-energy conformation, when the local pH drops, the protein undergoes an energetically favorable conformational rearrangement that enables it to penetrate the host cell membrane. Some tertiary protein structures may exist in long-lived states that are not the expected most stable state, for example, many serpiginouss show this metastability. They undergo a change when a loop of the protein is cut by a protease. Prediction of protein tertiary structure relies on knowing the primary structure
30.
Covalent bond
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A covalent bond, also called a molecular bond, is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs, for many molecules, the sharing of electrons allows each atom to attain the equivalent of a full outer shell, corresponding to a stable electronic configuration. Covalent bonding includes many kinds of interactions, including σ-bonding, π-bonding, metal-to-metal bonding, agostic interactions, bent bonds, the term covalent bond dates from 1939. In the molecule H2, the atoms share the two electrons via covalent bonding. Covalency is greatest between atoms of similar electronegativities, thus, covalent bonding does not necessarily require that the two atoms be of the same elements, only that they be of comparable electronegativity. Covalent bonding that entails sharing of electrons more than two atoms is said to be delocalized. The term covalence in regard to bonding was first used in 1919 by Irving Langmuir in a Journal of the American Chemical Society article entitled The Arrangement of Electrons in Atoms and Molecules. Langmuir wrote that we shall denote by the term covalence the number of pairs of electrons that an atom shares with its neighbors. The idea of covalent bonding can be traced several years before 1919 to Gilbert N. Lewis and he introduced the Lewis notation or electron dot notation or Lewis dot structure, in which valence electrons are represented as dots around the atomic symbols. Pairs of electrons located between atoms represent covalent bonds, multiple pairs represent multiple bonds, such as double bonds and triple bonds. An alternative form of representation, not shown here, has bond-forming electron pairs represented as solid lines, Lewis proposed that an atom forms enough covalent bonds to form a full outer electron shell. In the diagram of methane shown here, the atom has a valence of four and is, therefore, surrounded by eight electrons, four from the carbon itself. Each hydrogen has a valence of one and is surrounded by two electrons – its own one electron plus one from the carbon, walter Heitler and Fritz London are credited with the first successful quantum mechanical explanation of a chemical bond in 1927. Their work was based on the valence bond model, which assumes that a bond is formed when there is good overlap between the atomic orbitals of participating atoms. Atomic orbitals have specific directional properties leading to different types of covalent bonds, sigma bonds are the strongest covalent bonds and are due to head-on overlapping of orbitals on two different atoms. A single bond is usually a σ bond, pi bonds are weaker and are due to lateral overlap between p orbitals. A double bond between two given atoms consists of one σ and one π bond, and a bond is one σ. Covalent bonds are also affected by the electronegativity of the atoms which determines the chemical polarity of the bond
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Disulfide
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In chemistry, a disulfide refers to a functional group with the structure R–S–S–R. The linkage is called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. The connection is a persulfide, in analogy to its congener, peroxide, in inorganic chemistry disulfide usually refers to the corresponding anion S2−2, for example in disulfur dichloride. The disulfide bonds are strong, with a bond dissociation energy of 60 kcal/mol. However, being about 40% weaker than C–C and C–H bonds, rotation about the S–S axis is subject to a low barrier. Disulfides show a preference for dihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant, disulfides where the two R groups are the same are called symmetric, examples being diphenyl disulfide and dimethyl disulfide. When the two R groups are not identical, the compound is said to be an asymmetric or mixed disulfide, by comparison, the standard reduction potential for ferrodoxins is about −430 mV. Disulfide bonds are formed from the oxidation of sulfhydryl groups. The transformation is depicted as follows,2 RSH ⇌ RS–SR +2 H+ +2 e− A variety of oxidants promote this reaction including air, such reactions are thought to proceed via sulfenic acid intermediates. In the laboratory, iodine in the presence of base is employed to oxidize thiols to disulfides. Several metals, such as copper and iron complexes affect this reaction, the alkylation of alkali metal di- and polysulfides gives disulfides. Thiokol polymers arise when sodium polysulfide is treated with an alkyl dihalide, in the converse reaction, carbanionic reagents react with elemental sulfur to afford mixtures of the thioether, disulfide, and higher polysulfides. These reactions are often unselective but can be optimized for specific applications, many specialized methods have been developed for forming disulfides, usually for applications in organic synthesis. A variety of reductants can be used, furthermore, it is often not needed to remove TCEP before modification of protein thiols. In organic synthesis, hydride agents are employed for scission of disulfides. The original disulfide bond is broken, and its other sulfur atom is released as a new thiolate, meanwhile, a new disulfide bond forms between the attacking thiolate and the original sulfur atom. Thiolates, not thiols, attack disulfide bonds, hence, thiol–disulfide exchange is inhibited at low pH where the protonated thiol form is favored relative to the deprotonated thiolate form
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Cysteine
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Cysteine is a semi-essential proteinogenic amino acid with the formula HO2CCHCH2SH. It is encoded by the codons UGU and UGC, the thiol side chain in cysteine often participates in enzymatic reactions, as a nucleophile. The thiol is susceptible to oxidization to give the disulfide derivative cystine, when used as a food additive, it has the E number E920. It can be seen as serine, but with one of the oxygen replaced with sulfur. Cysteine can usually be synthesized by the body under normal physiological conditions if a sufficient quantity of methionine is available. Cysteine is catabolized in the tract and blood plasma. In contrast, cystine travels safely through the GI tract and blood plasma and is reduced to the two cysteine molecules upon cell entry. Like other amino acids, cysteine has an amphoteric character, the majority of L-cysteine is obtained industrially by hydrolysis of animal materials, such as poultry feathers or hog hair. Despite widespread belief otherwise, there is evidence that human hair is used as a source material. Synthetically produced L-cysteine, compliant with Jewish kosher and Muslim halal laws, is also available, the synthetic route involves fermentation using a mutant of E. coli. Degussa introduced a route from substituted thiazolines, following this technology, L-cysteine is produced by the hydrolysis of racemic 2-amino-Δ2-thiazoline-4-carboxylic acid using Pseudomonas thiazolinophilum. In animals, biosynthesis begins with the amino acid serine, the sulfur is derived from methionine, which is converted to homocysteine through the intermediate S-adenosylmethionine. Cystathionine beta-synthase then combines homocysteine and serine to form the asymmetrical thioether cystathionine, the enzyme cystathionine gamma-lyase converts the cystathionine into cysteine and alpha-ketobutyrate. In plants and bacteria, cysteine biosynthesis also starts from serine, the enzyme O-acetylserine -lyase, using sulfide sources, converts this ester into cysteine, releasing acetate. The cysteine thiol group is nucleophilic and easily oxidized, the reactivity is enhanced when the thiol is ionized, and cysteine residues in proteins have pKa values close to neutrality, so are often in their reactive thiolate form in the cell. Because of its reactivity, the thiol group of cysteine has numerous biological functions. Due to the ability of thiols to undergo reactions, cysteine has antioxidant properties. Cysteines antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms, the systemic availability of oral glutathione is negligible, so it must be biosynthesized from its constituent amino acids, cysteine, glycine, and glutamic acid
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Protein quaternary structure
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Protein quaternary structure is the number and arrangement of multiple folded protein subunits in a multi-subunit complex. It includes organisations from simple dimers to large homooligomers and complexes with defined or variable numbers of subunits and it can also refer to biomolecular complexes of proteins with nucleic acids and other cofactors. Many proteins are actually assemblies of multiple polypeptide chains, the quaternary structure refers to the number and arrangement of the protein subunits with respect to one another. Examples of proteins with quaternary structure include hemoglobin, DNA polymerase, other assemblies referred to instead as multiprotein complexes also possess quaternary structure. Changes in quaternary structure can occur through conformational changes within individual subunits or through reorientation of the relative to each other. It is through such changes, which underlie cooperativity and allostery in multimeric enzymes, the above definition follows a classical approach to biochemistry, established at times when the distinction between a protein and a functional, proteinaceous unit was difficult to elucidate. More recently, people refer to protein–protein interaction when discussing quaternary structure of proteins, the number of subunits in an oligomeric complex is described using names that end in -mer. *No known examples Although complexes higher than octamers are rarely observed for most proteins, viral capsids are often composed of multiples of 60 proteins. Several molecular machines are found in the cell, such as the proteasome, the transcription complex. The ribosome is probably the largest molecular machine, and is composed of many RNA, in some cases, proteins form complexes that then assemble into even larger complexes. In such cases, one uses the nomenclature, e. g. dimer of dimers or trimer of dimers, Protein quaternary structure can be determined using a variety of experimental techniques that require a sample of protein in a variety of experimental conditions. It is not always possible to obtain a precise determination of the composition for a variety of reasons. The number of subunits in a complex can often be determined by measuring the hydrodynamic molecular volume or mass of the intact complex. For folded proteins, the mass can be inferred from its volume using the specific volume of 0.73 ml/g. Some bioinformatics methods were developed for predicting the quaternary structural attributes of proteins based on their information by using various modes of pseudo amino acid composition. However, these may sometimes be applicable, for example, the experimenter may apply SDS-PAGE after first treating the complex with chemical cross-link reagents. Proteins are capable of forming very tight complexes, for example, ribonuclease inhibitor binds to ribonuclease A with a roughly 20 fM dissociation constant. Other proteins have evolved to specifically to unusual moieties on another protein, e. g. biotin groups
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N-terminus
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The N-terminus is the start of a protein or polypeptide terminated by an amino acid with a free amine group. By convention, peptide sequences are written N-terminus to C-terminus, left to right in LTR languages and this correlates the translation direction to the text direction. Each amino acid has a group and a carboxylic group. The chain has two ends - an amine group, the N-terminus, and a carboxyl group, the C-terminus. When a protein is translated from messenger RNA, it is created from N-terminus to C-terminus, the amino end of an amino acid during the elongation stage of translation, attaches to the carboxyl end of the growing chain. Since the start codon of the genetic codes for the amino acid methionine. However, some proteins are modified posttranslationally, for example, by cleavage from a protein precursor, the N-terminus is the first part of the protein that exits the ribosome during protein biosynthesis. It often contains signal peptide sequences, intracellular postal codes that direct delivery of the protein to the proper organelle, the signal peptide is typically removed at the destination by a signal peptidase. The N-terminal amino acid of a protein is an important determinant of its half-life and this is called the N-end rule. The N-terminal signal peptide is recognized by the signal recognition particle, in eukaryotic cells, these proteins are synthesized at the rough endoplasmic reticulum. In prokaryotic cells, the proteins are exported across the cell membrane, in chloroplasts, signal peptides target proteins to the thylakoids. The N-terminal mitochondrial targeting peptide allows for the protein to be imported into the mitochondrion, the N-terminal chloroplast targeting peptide allows for the protein to be imported into the chloroplast. Protein N-termini can be modified co - or posttranslationally and it has been suggested that N-terminal acetylation can prevent a protein from following a secretory pathway. The N-terminus can be modified by the addition of a myristoyl anchor, proteins that are modified this way contain a consensus motif at their N-terminus as a modification signal. The N-terminus can also be modified by the addition of a fatty acid anchor to form N-acylated proteins, the most common form of such modification is the addition of a palmitoyl group. TopFIND, a database covering proteases, their cleavage site specificity, substrates, inhibitors
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C-terminus
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The C-terminus is the end of an amino acid chain, terminated by a free carboxyl group. When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus, the convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Each amino acid has a group and an amine group. Amino acids link to one another to form a chain by a reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with a carboxyl group, the C-terminus, and an end with an unbound amine group. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus, while the N-terminus of a protein often contains targeting signals, the C-terminus can contain retention signals for protein sorting. The most common ER retention signal is the amino acid sequence -KDEL or -HDEL at the C-terminus and this keeps the protein in the endoplasmic reticulum and prevents it from entering the secretory pathway. One form of C-terminal modification is prenylation, during prenylation, a farnesyl- or geranylgeranyl-isoprenoid membrane anchor is added to a cysteine residue near the C-terminus. Small, membrane-bound G proteins are modified this way. Another form of C-terminal modification is the addition of a phosphoglycan, glycosylphosphatidylinositol, the GPI anchor is attached to the C-terminus after proteolytic cleavage of a C-terminal propeptide. The most prominent example for this type of modification is the prion protein, the C-terminal domain of some proteins has specialized functions. In humans, the CTD of RNA polymerase II typically consists of up to 52 repeats of the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser and this allows other proteins to bind to the C-terminal domain of RNA polymerase in order to activate polymerase activity. These domains then involved in the initiation of DNA transcription, the capping of the RNA transcript, N-terminus TopFIND, a scientific database covering proteases, their cleavage site specificity, substrates, inhibitors and protein termini originating from their activity
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Protein biosynthesis
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Protein synthesis is the process whereby biological cells generate new proteins, it is balanced by the loss of cellular proteins via degradation or export. Protein biosynthesis is regulated at multiple steps. They are principally during transcription and translation, the cistron DNA is transcribed into the first of a series of RNA intermediates. The last version is used as a template in synthesis of a polypeptide chain, Protein will often be synthesized directly from genes by translating mRNA. However, when a protein must be available on short notice or in large quantities, a proprotein is an inactive protein containing one or more inhibitory peptides that can be activated when the inhibitory sequence is removed by proteolysis during posttranslational modification. A preprotein is a form that contains a sequence that specifies its insertion into or through membranes. The signal peptide is cleaved off in the endoplasmic reticulum, preproproteins have both sequences still present. The amino acids are linked together to extend the growing protein chain. This whole complex of processes is carried out by the ribosome, the ribosome latches onto the end of an mRNA molecule and moves along it, capturing loaded tRNA molecules and joining together their amino acids to form a new protein chain. Protein biosynthesis, although similar, is different for prokaryotes and eukaryotes. In transcription an mRNA chain is generated, with one strand of the DNA double helix in the genome as a template and this strand is called the template strand. Transcription occurs in the nucleus, where the DNA is held. The DNA structure of the cell is made up of two made up of sugar and phosphate held together by hydrogen bonds between the bases of opposite strands. The sugar and the phosphate in each strand are joined together by stronger covalent bonds. The DNA is unzipped by the helicase, leaving the single nucleotide chain open to be copied. RNA polymerase reads the DNA strand from the 3-prime end to the 5-prime end, the general RNA structure is very similar to the DNA structure, but in RNA the nucleotide uracil takes the place that thymine occupies in DNA. The single strand of mRNA leaves the nucleus through nuclear pores, hnRNA then undergoes splicing of introns via spliceosomes to produce the final mRNA. The synthesis of proteins from RNA is known as translation, in eukaryotes, translation occurs in the cytoplasm, where the ribosomes are located
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Macromolecule
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A macromolecule is a very large molecule, such as protein, commonly created by polymerization of smaller subunits. They are typically composed of thousands of atoms or more, the most common macromolecules in biochemistry are biopolymers and large non-polymeric molecules. Synthetic macromolecules include common plastics and synthetic fibres as well as materials such as carbon nanotubes. The term macromolecule was coined by Nobel laureate Hermann Staudinger in the 1920s, usage of the term to describe large molecules varies among the disciplines. According to the standard IUPAC definition, the term macromolecule as used in science refers only to a single molecule. For example, a polymeric molecule is appropriately described as a macromolecule or polymer molecule rather than a polymer. Because of their size, macromolecules are not conveniently described in terms of stoichiometry alone, the structure of simple macromolecules, such as homopolymers, may be described in terms of the individual monomer subunit and total molecular mass. Complicated biomacromolecules, on the hand, require multi-faceted structural description such as the hierarchy of structures used to describe proteins. In British English. Macromolecules often have physical properties that do not occur for smaller molecules. For example, DNA in a solution can be simply by sucking the solution through an ordinary straw because the physical forces on the molecule can overcome the strength of its covalent bonds. The 1964 edition of Linus Paulings College Chemistry asserted that DNA in nature is never longer than about 5,000 base pairs and this error arose because biochemists were inadvertently breaking their samples into fragments. In fact, the DNA of chromosomes can be hundreds of millions of base pairs long, another common macromolecular property that does not characterize smaller molecules is their relative insolubility in water and similar solvents, instead forming colloids. Many require salts or particular ions to dissolve in water, similarly, many proteins will denature if the solute concentration of their solution is too high or too low. High concentrations of macromolecules in a solution can alter the rates and equilibrium constants of the reactions of other macromolecules and this comes from macromolecules excluding other molecules from a large part of the volume of the solution, thereby increasing the effective concentrations of these molecules. All living organisms are dependent on three essential biopolymers for their functions, DNA, RNA and Proteins. Each of these molecules is required for life since each plays a distinct, the simple summary is that DNA makes RNA, and then RNA makes proteins. DNA, RNA and proteins all consist of a structure of related building blocks. In general, they are all unbranched polymers, and so can be represented in the form of a string
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Self-assembly
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When the constitutive components are molecules, the process is termed molecular self-assembly. Self-assembly can be classified as either static or dynamic, in static self-assembly, the ordered state forms as a system approaches equilibrium, reducing its free energy. These structures are described as self-organized. Self-assembly in the classic sense can be defined as the spontaneous, self-assembled nano-structure is an object that appears as a result of ordering and aggregation of individual nano-scale objects guided by some physical principle. Self-assembled nanostructure arises in the strong non-equilibrium conditions, the most famous example of self-assembly phenomenon is the occurrence of the life on Earth. It is plausible to hypothesize that it happens because the sun generates a strong gradient in its environment. This general idea has been confirmed in the experiment of self-assembly of carbon nanotubes, another interesting example of self-assembly is the phenomenon of electrostatic trapping. In this case a field is applied between two metallic nano-electrodes. The particles present in the environment are polarized by the electric field. Due to dipole interaction with the field gradient the particles are attracted to the gap between the electrodes. Fabricating a crystal by placing atom after atom is not realistic, however self-assembly of crystals works well. Similarly fabricating a 3D nano-structure is not realistic as well, self-assembly of 3D nano-structure becomes an easy and inexpensive way to fabricate them. Nano-structures such as gaps are used for storing energy and nuclear energy conversion. Self-assembled tunable materials are promising candidates for large surface area electrodes in batteries and organic photovoltaic cells, at this point, one may argue that any chemical reaction driving atoms and molecules to assemble into larger structures, such as precipitation, could fall into the category of SA. However, there are at least three distinctive features that make SA a distinct concept, first, the self-assembled structure must have a higher order than the isolated components, be it a shape or a particular task that the self-assembled entity may perform. This is generally not true in chemical reactions, where a state may proceed towards a disordered state depending on thermodynamic parameters. The second important aspect of SA is the key role of interactions with respect to more traditional covalent, ionic. Although typically less energetic by a factor of 10, these interactions play an important role in materials synthesis
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Water
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Water is a transparent and nearly colorless chemical substance that is the main constituent of Earths streams, lakes, and oceans, and the fluids of most living organisms. Its chemical formula is H2O, meaning that its molecule contains one oxygen, Water strictly refers to the liquid state of that substance, that prevails at standard ambient temperature and pressure, but it often refers also to its solid state or its gaseous state. It also occurs in nature as snow, glaciers, ice packs and icebergs, clouds, fog, dew, aquifers, Water covers 71% of the Earths surface. It is vital for all forms of life. Only 2. 5% of this water is freshwater, and 98. 8% of that water is in ice and groundwater. Less than 0. 3% of all freshwater is in rivers, lakes, and the atmosphere, a greater quantity of water is found in the earths interior. Water on Earth moves continually through the cycle of evaporation and transpiration, condensation, precipitation. Evaporation and transpiration contribute to the precipitation over land, large amounts of water are also chemically combined or adsorbed in hydrated minerals. Safe drinking water is essential to humans and other even though it provides no calories or organic nutrients. There is a correlation between access to safe water and gross domestic product per capita. However, some observers have estimated that by 2025 more than half of the population will be facing water-based vulnerability. A report, issued in November 2009, suggests that by 2030, in developing regions of the world. Water plays an important role in the world economy, approximately 70% of the freshwater used by humans goes to agriculture. Fishing in salt and fresh water bodies is a source of food for many parts of the world. Much of long-distance trade of commodities and manufactured products is transported by boats through seas, rivers, lakes, large quantities of water, ice, and steam are used for cooling and heating, in industry and homes. Water is an excellent solvent for a variety of chemical substances, as such it is widely used in industrial processes. Water is also central to many sports and other forms of entertainment, such as swimming, pleasure boating, boat racing, surfing, sport fishing, Water is a liquid at the temperatures and pressures that are most adequate for life. Specifically, at atmospheric pressure of 1 bar, water is a liquid between the temperatures of 273.15 K and 373.15 K
. PMID 4565129.