1.
Myoglobin
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Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, in humans, myoglobin is only found in the bloodstream after muscle injury. It is a finding, and can be diagnostically relevant when found in blood. Myoglobin is the primary oxygen-carrying pigment of muscle tissues, high concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with high abundance of myoglobin. Myoglobin is found in Type I muscle, Type II A and Type II B, myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography. This achievement was reported in 1958 by John Kendrew and associates, for this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. They adapted to this deficiency through natural reactions to inadequate oxygen supply, in humans myoglobin is encoded by the MB gene. Hemoglobin can take the forms of oxyhemoglobin, carboxyhemoglobin, and methemoglobin, similarly, myoglobin can take the forms of oxymyoglobin, carboxymyoglobin, like hemoglobin, myoglobin is a cytoplasmic protein that binds oxygen on a heme group. It harbors only one group, whereas hemoglobin has four. Although its heme group is identical to those in Hb, Mb has an affinity for oxygen than does hemoglobin. This difference is related to its different role, whereas hemoglobin transports oxygen, myoglobin contains hemes, pigments responsible for the colour of red meat. The colour that meat takes is partly determined by the degree of oxidation of the myoglobin, in fresh meat the iron atom is the ferrous oxidation state bound to an oxygen molecule. Meat cooked well done is brown because the atom is now in the ferric oxidation state. If meat has been exposed to nitrites, it will remain pink because the atom is bound to NO. Grilled meats can also take on a smoke ring that comes from the iron binding to a molecule of carbon monoxide. Raw meat packed in a carbon monoxide atmosphere also shows this same pink smoke ring due to the same principles, notably, the surface of this raw meat also displays the pink color, which is usually associated in consumers minds with fresh meat. This artificially induced pink color can persist, reportedly up to one year, hormel and Cargill are both reported to use this meat-packing process, and meat treated this way has been in the consumer market since 2003
2.
Heme
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Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group, these are known as hemoproteins. Hemoproteins have diverse functions including the transportation of diatomic gases, chemical catalysis, diatomic gas detection. The heme iron serves as a source or sink of electrons during electron transfer or redox chemistry, in peroxidase reactions, the porphyrin molecule also serves as an electron source. In the transportation or detection of gases, the gas binds to the heme iron. During the detection of gases, the binding of the gas ligand to the heme iron induces conformational changes in the surrounding protein. Hemoproteins achieve their remarkable diversity by modifying the environment of the heme macrocycle within the protein matrix. For example, the ability of hemoglobin to effectively deliver oxygen to tissues is due to amino acid residues located near the heme molecule. Hemoglobin reversibly binds to oxygen in the lungs when the pH is high, when the situation is reversed, hemoglobin will release oxygen into the tissues. This phenomenon, which states that hemoglobins oxygen binding affinity is inversely proportional to both acidity and concentration of carbon dioxide, is known as the Bohr effect. There are several biologically important kinds of heme, The most common type is heme B, other important types include heme A, isolated hemes are commonly designated by capital letters while hemes bound to proteins are designated by lower case letters. Cytochrome a refers to the heme A in specific combination with membrane protein forming a portion of cytochrome c oxidase, the following carbon numbering system of porphyrins is an older numbering used by biochemists and not the 1–24 numbering system recommended by IUPAC which is shown in the table above. Heme l is the derivative of heme B which is attached to the protein of lactoperoxidase, eosinophil peroxidase. The addition of peroxide with the glutamyl-375 and aspartyl-225 of lactoperoxidase forms ester bonds between amino acid residues and the heme 1- and 5-methyl groups, respectively. Similar ester bonds with two methyl groups are thought to form in eosinophil and thyroid peroxidases. Heme l is one important characteristic of animal peroxidases, plant peroxidases incorporate heme B, lactoperoxidase and eosinophil peroxidase are protective enzymes responsible for the destruction of invading bacteria and virus. Thyroid peroxidase is the enzyme catalyzing the biosynthesis of the important thyroid hormones, because lactoperoxidase destroys invading organisms in the lungs and excrement, it is thought to be an important protective enzyme. Heme m is the derivative of heme B covalently bound at the site of myeloperoxidase. Heme m contains the two ester bonds at the heme 1- and 5-methyls as in heme l found in other mammalian peroxidases, myeloperoxidase is present in mammalian neutrophils and is responsible for the destruction of invading bacteria and viruse
3.
Oxygen
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Oxygen is a chemical element with symbol O and atomic number 8. It is a member of the group on the periodic table and is a highly reactive nonmetal. By mass, oxygen is the third-most abundant element in the universe, after hydrogen, at standard temperature and pressure, two atoms of the element bind to form dioxygen, a colorless and odorless diatomic gas with the formula O2. This is an important part of the atmosphere and diatomic oxygen gas constitutes 20. 8% of the Earths atmosphere, additionally, as oxides the element makes up almost half of the Earths crust. Most of the mass of living organisms is oxygen as a component of water, conversely, oxygen is continuously replenished by photosynthesis, which uses the energy of sunlight to produce oxygen from water and carbon dioxide. Oxygen is too reactive to remain a free element in air without being continuously replenished by the photosynthetic action of living organisms. Another form of oxygen, ozone, strongly absorbs ultraviolet UVB radiation, but ozone is a pollutant near the surface where it is a by-product of smog. At low earth orbit altitudes, sufficient atomic oxygen is present to cause corrosion of spacecraft, the name oxygen was coined in 1777 by Antoine Lavoisier, whose experiments with oxygen helped to discredit the then-popular phlogiston theory of combustion and corrosion. One of the first known experiments on the relationship between combustion and air was conducted by the 2nd century BCE Greek writer on mechanics, Philo of Byzantium. In his work Pneumatica, Philo observed that inverting a vessel over a burning candle, Philo incorrectly surmised that parts of the air in the vessel were converted into the classical element fire and thus were able to escape through pores in the glass. Many centuries later Leonardo da Vinci built on Philos work by observing that a portion of air is consumed during combustion and respiration, Oxygen was discovered by the Polish alchemist Sendivogius, who considered it the philosophers stone. In the late 17th century, Robert Boyle proved that air is necessary for combustion, English chemist John Mayow refined this work by showing that fire requires only a part of air that he called spiritus nitroaereus. From this he surmised that nitroaereus is consumed in both respiration and combustion, Mayow observed that antimony increased in weight when heated, and inferred that the nitroaereus must have combined with it. Accounts of these and other experiments and ideas were published in 1668 in his work Tractatus duo in the tract De respiratione. Robert Hooke, Ole Borch, Mikhail Lomonosov, and Pierre Bayen all produced oxygen in experiments in the 17th and the 18th century but none of them recognized it as a chemical element. This may have been in part due to the prevalence of the philosophy of combustion and corrosion called the phlogiston theory, which was then the favored explanation of those processes. Established in 1667 by the German alchemist J. J. Becher, one part, called phlogiston, was given off when the substance containing it was burned, while the dephlogisticated part was thought to be its true form, or calx. The fact that a substance like wood gains overall weight in burning was hidden by the buoyancy of the combustion products
4.
Protein Data Bank
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The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
5.
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
6.
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
7.
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
8.
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°
9.
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
10.
Triosephosphate isomerase
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Triose-phosphate isomerase is an enzyme that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate. Compound C00111 at KEGG Pathway Database. Enzyme 5.3.1.1 at KEGG Pathway Database. Compound C00118 at KEGG Pathway Database, TPI plays an important role in glycolysis and is essential for efficient energy production. TPI has been found in every organism searched for the enzyme, including animals such as mammals and insects as well as in fungi, plants. However, some bacteria that do not perform glycolysis, like ureaplasmas, in humans, deficiencies in TPI are associated with a progressive, severe neurological disorder called triose phosphate isomerase deficiency. Triose phosphate isomerase deficiency is characterized by hemolytic anemia. While there are mutations that cause this disease, most include the mutation of glutamic acid at position 104 to aspartic acid. Triose phosphate isomerase is an efficient enzyme, performing the reaction billions of times faster than it would occur naturally in solution. The reaction is so efficient that it is said to be perfect, It is limited only by the rate the substrate can diffuse into. The mechanism involves the formation of an enediol. The relative free energy of each state and transition state has been determined experimentally. The structure of TPI facilitates the conversion between dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, the nucleophilic glutamate 165 residue of TPI deprotonates the substrate, and the electrophilic histidine 95 residue donates a proton to form the enediol intermediate. When deprotonated, the enediolate then collapses and, abstracting a proton from protonated glutamate 165, catalysis of the reverse reaction proceeds analogously, forming the same enediol but with enediolate collapse from the oxygen at C2. In terms of thermodynamics, DHAP formation is favored 20,1 over GAP production, however, in glycolysis, the use of GAP in the subsequent steps of metabolism drives the reaction toward its production. TPI is inhibited by sulfate, phosphate, and arsenate ions, other inhibitors include 2-phosphoglycolate, a transition state analog, and D-glycerol-1-phosphate, a substrate analog. Triose phosphate isomerase is a dimer of identical subunits, each of which is made up of about 250 amino acid residues, the three-dimensional structure of a subunit contains eight α-helices on the outside and eight parallel β-strands on the inside. In the illustration, the backbone of each subunit is colored in blue to red from N-terminus to C-terminus. This structural motif is called an αβ-barrel, or a TIM-barrel, the active site of this enzyme is in the center of the barrel. A glutamic acid residue and a histidine are involved in the catalytic mechanism, the sequence around the active site residues is conserved in all known triose phosphate isomerases
, PMID 1304880
