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 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 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 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
Chloroplasts /ˈklɔːrəˌplæsts, -plɑːsts/ are organelles, specialized subunits, in plant and algal cells. Their discovery inside plant cells is usually credited to Julius von Sachs and they use the ATP and NADPH to make organic molecules from carbon dioxide in a process known as the Calvin cycle. Chloroplasts carry out a number of functions, including fatty acid synthesis, much amino acid synthesis. The number of chloroplasts per cell varies from one, in algae, up to 100 in plants like Arabidopsis. A chloroplast is a type of known as a plastid. Other plastid types, such as the leucoplast and the chromoplast, contain little chlorophyll, chloroplasts are highly dynamic—they circulate and are moved around within plant cells, and occasionally pinch in two to reproduce. Their behavior is influenced by environmental factors like light color. Chloroplasts, like mitochondria, contain their own DNA, which is thought to be inherited from their ancestor—a photosynthetic cyanobacterium that was engulfed by a eukaryotic cell.
Chloroplasts cannot be made by the plant cell and must be inherited by each cell during cell division. With one exception, all chloroplasts can probably be traced back to a single endosymbiotic event, despite this, chloroplasts can be found in an extremely wide set of organisms, some not even directly related to each other—a consequence of many secondary and even tertiary endosymbiotic events. The word chloroplast is derived from the Greek words chloros, which means green, and plastes, the first definitive description of a chloroplast was given by Hugo von Mohl in 1837 as discrete bodies within the green plant cell. In 1883, A. F. W. Schimper would name these bodies as chloroplastids, in 1884, Eduard Strasburger adopted the term chloroplasts. Chloroplasts are one of many types of organelles in the plant cell and they are considered to have originated from cyanobacteria through endosymbiosis—when a eukaryotic cell engulfed a photosynthesizing cyanobacterium that became a permanent resident in the cell.
Mitochondria are thought to have come from an event, where an aerobic prokaryote was engulfed. This origin of chloroplasts was first suggested by the Russian biologist Konstantin Mereschkowski in 1905 after Andreas Schimper observed in 1883 that chloroplasts closely resemble cyanobacteria, chloroplasts are only found in plants and the amoeboid Paulinella chromatophora. Cyanobacteria are considered the ancestors of chloroplasts and they are sometimes called blue-green algae even though they are prokaryotes. They are a phylum of bacteria capable of carrying out photosynthesis. Cyanobacteria contain a cell wall, which is thicker than in other gram-negative bacteria
In biology, homology is the existence of shared ancestry between a pair of structures, or genes, in different taxa. Evolutionary biology explains homologous structures adapted to different purposes as the result of descent with modification from a common ancestor, examples include the legs of a centipede, the maxillary palp and labial palp of an insect, and the spinous processes of successive vertebrae in a vertebral column. Sequence homology between protein or DNA sequences is defined in terms of shared ancestry. Two segments of DNA can have shared ancestry because of either an event or a duplication event. Homology among proteins or DNA is inferred from their sequence similarity, significant similarity is strong evidence that two sequences are related by divergent evolution from a common ancestor. Alignments of multiple sequences are used to discover the homologous regions, the word homology, coined in about 1656, derives from the Greek ὁμόλογος homologos from ὁμός homos same and λόγος logos relation.
Homology is the relationship between biological structures or sequences that are derived from a common ancestor, for example, many insects possess two pairs of flying wings. In beetles, the first pair of wings has evolved into a pair of hard wing covers, the same major forearm bones are found in fossils of lobe-finned fish such as Eusthenopteron. The opposite of homologous organs are analogous organs which do similar jobs in two taxa that were not present in their last common ancestor but rather evolved separately. For example, the wings of insects and birds evolved independently in widely separated groups, the wings of a sycamore maple seed and the wings of a bird are analogous but not homologous, as they develop from quite different structures. A structure can be homologous at one level, but only analogous at another, for example, in the pterosaurs, the wing involves both the forelimb and the hindlimb. Analogy is called homoplasy in cladistics, and convergent or parallel evolution in evolutionary biology, specialised terms are used in taxonomic research.
Primary homology is that initially conjectured by a researcher based on similar structure or anatomical connections, secondary homology is implied by parsimony analysis, where a character that only occurs once on a tree is taken to be homologous. As implied in this definition, many cladists consider homology to be synonymous with synapomorphy, homologies provide the fundamental basis for all biological classification, although some may be highly counter-intuitive. The homologies between these have been discovered by comparing genes in evolutionary developmental biology, among insects, the stinger of the female honey bee is a modified ovipositor, homologous with ovipositors in other insects such as the Orthoptera and those Hymenoptera without stingers. The three small bones in the ear of mammals including humans, the malleus, incus. The malleus and incus develop in the embryo from structures that form jaw bones in lizards, both lines of evidence show that these bones are homologous, sharing a common ancestor.
Among the many homologies in mammal reproductive systems and testicles are homologous, in many plants, defensive or storage structures are made by modifications of the development of primary leaves and roots
This secondary structure is sometimes called a classic Pauling–Corey–Branson α-helix. The name 3. 613-helix is 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 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 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°
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the protein components of chromatin, acting as spools around which DNA winds. Without histones, the unwound DNA in chromosomes would be very long, five major families of histones exist, H1/H5, H2A, H2B, H3, and H4. Histones H2A, H2B, H3 and H4 are known as the core histones, the core histones all exist as dimers, which are similar in that they all possess the histone fold domain, three alpha helices linked by two loops. It is this structure that allows for interaction between distinct dimers, particularly in a head-tail fashion. The resulting four distinct dimers come together to form one octameric nucleosome core, around 146 base pairs of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn to give a particle of around 100 Angstroms across. The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place, the most basic such formation is the 10 nm fiber or beads on a string conformation.
This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA separating each pair of nucleosomes, higher-order structures include the 30 nm fiber and 100 nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the chromosomes are assembled through interactions between nucleosomes and other regulatory proteins. In animals, genes encoding canonical histones are typically clustered along the chromosome, lack introns, genes encoding histone variants are usually not clustered, have introns and their mRNAs are regulated with polyA tails. Complex multicellular organisms typically have a number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the links between variants and the delicate regulation of organism development. Histone variants from different organisms, their classification and variant specific features can be found in HistoneDB2.0 - Variants database.
The following is a list of human proteins, The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure. The H2A-H2B dimers and H3-H4 tetramer show pseudodyad symmetry, the 4 core histones are relatively similar in structure and are highly conserved through evolution, all featuring a helix turn helix turn helix motif. They share the feature of long tails on one end of the amino acid structure - this being the location of post-translational modification, despite the differences in their topology, these three folds share a homologous helix-strand-helix motif. Using an electron paramagnetic resonance spin-labeling technique, British researchers measured the distances between the spools around which eukaryotic cells wind their DNA and they determined the spacings range from 59 to 70 Å. Histones are subject to post translational modification by enzymes primarily on their N-terminal tails, such modifications include methylation, acetylation, phosphorylation, SUMOylation, and ADP-ribosylation
Convergent evolution is the independent evolution of similar features in species of different lineages. Convergent evolution creates analogous structures that have similar form or function but were not present in the last common ancestor of those groups, the cladistic term for the same phenomenon is homoplasy. The recurrent evolution of flight is an example, as flying insects, birds. Functionally similar features that have arisen through convergent evolution are analogous, whereas homologous structures or traits have a common origin, bird and pterosaur wings are analogous structures, but their forelimbs are homologous, sharing an ancestral state despite serving different functions. The opposite of convergence is divergent evolution, where related species evolve different traits, convergent evolution is similar to but different from parallel evolution. Many instances of convergent evolution are known in plants, including the development of C4 photosynthesis, seed dispersal by fleshy fruits adapted to be eaten by animals.
In morphology, analogous traits arise when different species live in similar ways and/or a similar environment, when occupying similar ecological niches similar problems can lead to similar solutions. The British anatomist Richard Owen was the first to identify the difference between analogies and homologies. In biochemistry and chemical constraints on mechanisms have caused some active site arrangements such as the triad to evolve independently in separate enzyme superfamilies. In his 1989 book Wonderful Life, Stephen Jay Gould argued that if one could rewind the tape of life the same conditions were encountered again, evolution could take a very different course. In cladistics, a homoplasy is a trait shared by two or more taxa for any other than that they share a common ancestry. Taxa which do share ancestry are part of the same clade, homoplastic traits caused by convergence are therefore, from the point of view of cladistics, confounding factors which could lead to an incorrect analysis.
In some cases, it is difficult to tell whether a trait has been lost and re-evolved convergently, or whether a gene has simply been switched off, such a re-emerged trait is called an atavism. From a mathematical standpoint, a gene has a steadily decreasing probability of retaining potential functionality over time. When two species are similar in a character, evolution is defined as parallel if the ancestors were similar. When the ancestral forms are unspecified or unknown, or the range of traits considered is not clearly specified, the enzymology of proteases provides some of the clearest examples of convergent evolution. These examples reflect the intrinsic chemical constraints on enzymes, leading evolution to converge on equivalent solutions independently and repeatedly and cysteine proteases use different amino acid functional groups as a nucleophile. In order to activate that nucleophile, they orient an acidic, the chemical and physical constraints on enzyme catalysis have caused identical triad arrangements to evolve independently more than 20 times in different enzyme superfamilies
Neutral mutations are changes in DNA sequence that are neither beneficial nor detrimental to the ability of an organism to survive and reproduce. In population genetics, mutations in which natural selection does not affect the spread of the mutation in a species are termed neutral mutations, neutral mutations that are inheritable and not linked to any genes under selection will either be lost or will replace all other alleles of the gene. This loss or fixation of the gene proceeds based on random sampling known as genetic drift, a neutral mutation that is in linkage disequilibrium with other alleles that are under selection may proceed to loss or fixation via genetic hitchhiking and/or background selection. While many mutations in a genome may decrease an organism’s ability to survive and reproduce, known as fitness, the identification and study of neutral mutations has led to the development of the neutral theory of molecular evolution. Neutral mutations are the basis for using molecular clocks to identify such evolutionary events as speciation and adaptive or evolutionary radiations.
While Darwin is widely credited with introducing the idea of natural selection which was the focus of his studies, Darwins view of change being mostly driven by traits that provide advantage was widely accepted until the 1960s. However, Kimura explained this rapid rate of mutation by suggesting that the majority of mutations were neutral, Kimura developed mathematical models of the behavior of neutral mutations subject to random genetic drift in biological populations. This theory has become known as the theory of molecular evolution. As technology has allowed for better analysis of data, research has continued in this area. While natural selection may encourage adaptation to an environment, neutral mutation may push divergence of species due to nearly random genetic drift. Neutral mutation has become a part of the theory of molecular evolution. This theory suggests that mutations are responsible for a large portion of DNA sequence changes in a species. For example and human insulin, while differing in amino acid sequence are still able to perform the same function, the amino acid substitutions between species were seen therefore to be neutral or not impactful to the function of the protein.
Neutral mutation and the theory of molecular evolution are not separate from natural selection. Mutations can give an advantage, create a disadvantage, or make no difference to an organisms survival. These predictions have been confirmed with the introduction of genetic data since the theory’s introduction. When an incorrect nucleotide is inserted during replication or transcription of a coding region, since multiple codons are used for the same amino acids, a change in a single base may still lead to translation of the same amino acid. This phenomenon is referred to as degeneracy and allows for a variety of codon combinations leading to the amino acid being produced
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 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 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 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 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
A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a gene family. The term protein family should not be confused with family as it is used in taxonomy, proteins in a family descend from a common ancestor and typically have similar three-dimensional structures and significant sequence similarity. The most important of these is sequence similarity since it is the strictest indicator of homology, there is a fairly well developed framework for evaluating the significance of similarity between a group of sequences using sequence alignment methods. Families are sometimes grouped together into larger clades called superfamilies based on structural and mechanistic similarity, over 60,000 protein families have been defined, although ambiguity in the definition of protein family leads different researchers to wildly varying numbers. Other terms such as class, group and sub-family have been coined over the years. A common usage is that superfamilies contain families which contain sub-families, hence a superfamily, such as the PA clan of proteases, has far lower sequence conservation than one of the families it contains, the C04 family.
It is unlikely that an exact definition will be agreed and to it is up to the reader to discern exactly how these terms are being used in a particular context, since that time, it was found that many proteins comprise multiple independent structural and functional units or domains. Due to evolutionary shuffling, different domains in a protein have evolved independently and this has led, in recent years, to a focus on families of protein domains. A number of resources are devoted to identifying and cataloging such domains. Regions of each protein have differing functional constraints, for example, the active site of an enzyme requires certain amino acid residues to be precisely oriented in three dimensions. On the other hand, a protein–protein binding interface may consist of a surface with constraints on the hydrophobicity or polarity of the amino acid residues. These blocks are most commonly referred to as motifs, although other terms are used. Again, a number of online resources are devoted to identifying and cataloging protein motifs.
According to current consensus, protein families arise in two ways, the separation of a parent species into two genetically isolated descendent species allows a gene/protein to independently accumulate variations in these two lineages. This results in a family of proteins, usually with conserved sequence motifs. Secondly, a gene duplication may create a copy of a gene. Because the original gene is able to perform its function
Chymotrypsin is a digestive enzyme component of pancreatic juice acting in the duodenum where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side of the amide bond is a large hydrophobic amino acid. These amino acids contain a ring in their sidechain that fits into a hydrophobic pocket of the enzyme. It is activated in the presence of trypsin, the hydrophobic and shape complementarity between the peptide substrate P1 sidechain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin hydrolyzes other amide bonds in peptides at slower rates, structurally, it is the archetypal structure for its superfamily, the PA clan of proteases. Chymotrypsin is synthesized in the pancreas by protein biosynthesis as a precursor called chymotrypsinogen that is enzymatically inactive, trypsin activates chymotrypsinogen by cleaving peptidic bonds in positions Arg15 - Ile16 and produces π-Chymotrypsin.
In turn, aminic group of the Ile16 residue interacts with the chain of Glu194, producing the oxyanion hole. Moreover, Chymotrypsin induces its own activation by cleaving in positions 14-15, 146-147 and 148-149, the resulting molecule is a three-polypeptide molecule interconnected via disulfide bonds. In vivo, chymotrypsin is an enzyme acting in the digestive systems of many organisms. It facilitates the cleavage of bonds by a hydrolysis reaction. The main substrates of chymotrypsin include tryptophan, tyrosine and leucine, like many proteases, chymotrypsin will hydrolyse amide bonds in vitro, a virtue that enabled the use of substrate analogs such as N-acetyl-L-phenylalanine p-nitrophenyl amide for enzyme assays. Along with histidine 57 and aspartic acid 102, this serine residue constitutes the catalytic triad of the active site and it is called ping-pong mechanism. The mode of action of chymotrypsin explains this as hydrolysis takes place in two steps, first acylation of the substrate to form an acyl-enzyme intermediate and deacylation in order to return the enzyme to its original state.
This occurs via the action of the three amino acid residues in the catalytic triad. Aspartate hydrogen bonds to the N-δ hydrogen of histidine, increasing the pKa of its ε nitrogen and it is this deprotonation that allows the serine side chain to act as a nucleophile and bind to the electron-deficient carbonyl carbon of the protein main chain. Ionization of the oxygen is stabilized by formation of two hydrogen bonds to adjacent main chain N-hydrogens. This occurs in the oxyanion hole and this forms a tetrahedral adduct and breakage of the peptide bond. An acyl-enzyme intermediate, bound to the serine, is formed, in the second reaction step, a water molecule is activated by the basic histidine, and acts as a nucleophile.001 Chymotrypsin at the US National Library of Medicine Medical Subject Headings
Common names, Stejnegers pit viper, Chinese green tree viper, bamboo viper, Chinese tree viper, and others. Trimeresurus stejnegeri is a species of pit viper endemic to Asia. Three subspecies are recognized, including the nominate subspecies described here. The specific name, stejnegeri, is in honor of Leonhard Hess Stejneger, grows to a maximum total length of 75 centimetres, with a tail length of 14.5 centimetres. The males have hemipenes that are short and spinose beyond the bifurcation, dorsal scales in 21 longitudinal rows at midbody. 9-11 upper labials, of which the first are separated from nasal scales by a distinct suture, the supraoculars are single and sometimes divided by a transverse suture. There are 11-16 scales in a line between the supraoculars, the ventrals number 150-174, and the subcaudals are 54-77. All of the subcaudals are paired and Nepal through Burma and Laos to China and Taiwan. Leviton et al. mention Vietnam, the type locality was originally listed as Shaowu, Fukien Province and emended to N. W.
Fukien Province by Pope & Pope, the wound usually feels extremely painful, as if it had been branded with a hot iron, and the pain does not subside until about 24 hours after being bitten. Within a few minutes of being bitten, the surrounding flesh dies and turns black, the wound site quickly swells, and the skin and muscle become black due to necrosis. The size of the area depends on the amount of venom injected