Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins. Chemistry (from Greek χημεία khemeia[1] meaning alchemy) is the science of matter at the atomic to molecular scale, dealing primarily with collections of atoms, such as molecules, crystals, and metals. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Translation is the second process of protein biosynthesis (part of the overall process of gene expression). ... An overview of protein synthesis. ...

The bottom of this diagram shows the modification of primary structure of insulin, as described.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated in proteins. After translation, the posttranslational modification (PTM) of amino acids extends the range of functions of the protein by attaching to it other biochemical functional groups such as acetate, phosphate, various lipids and carbohydrates, by changing the chemical nature of an amino acid (e.g. citrullination) or by making structural changes, like the formation of disulfide bridges. Image File history File links Download high resolution version (1488x2105, 524 KB) Summary created by Isaac Yonemoto using Inkscape Licensing This image is licensed under the Creative Commons Attribution License v. ... Image File history File links Download high resolution version (1488x2105, 524 KB) Summary created by Isaac Yonemoto using Inkscape Licensing This image is licensed under the Creative Commons Attribution License v. ... A protein primary structure is a chain of amino acids. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ... The general structure of an amino acid molecule, with the amine group on the left and the carboxyl group on the right. ... In organic chemistry, functional groups are specific groups of atoms within molecules, that are responsible for the characteristic chemical reactions of those molecules. ... Acetate, or ethanoate, is the anion of a salt or ester of acetic acid. ... Above is a ball-and-stick model of the inorganic phosphate molecule (HPO42−). Colour coding: P (orange); O (red); H (white). ... Lipids are a class of hydrocarbon-containing organic compounds. ... Lactose is a disaccharide found in milk. ... The chemical compound citrulline is an α-amino acid (AA). ... A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ...

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... The N-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free amine group (NH2). ... A hormone (from Greek horman - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... It has been suggested that Oral insulin be merged into this article or section. ... A protein precursor is an inactive protein (or peptide) that can be turned into an active form by posttranslational modification. ...

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme. Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule. ...

PTMs involving addition of functional groups

PTMs involving addition include:

• acetylation, the addition of an acetyl group, usually at the N-terminus of the protein
• alkylation, the addition of an alkyl group (e.g. methyl, ethyl)
  • methylation the addition of a methyl group, usually at lysine or arginine residues. (This is a type of alkylation.)
• biotinylation, acylation of conserved lysine residues with a biotin appendage
• glutamylation, covalent linkage of glutamic acid residues to tubulin and some other proteins.
• glycylation, covalent linkage of one to more than 40 glycine residues to the tubulin C-terminal tail
• glycosylation, the addition of a glycosyl group to either asparagine, hydroxylysine, serine, or threonine, resulting in a glycoprotein
• isoprenylation, the addition of an isoprenoid group (e.g. farnesol and geranylgeraniol)
• lipoylation, attachment of a lipoate functionality
• phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from coenzyme A, as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis
• phosphorylation, the addition of a phosphate group, usually to serine, tyrosine, threonine or histidine
• sulfation, the addition of a sulfate group to a tyrosine.
• Selenation
• C-terminal amidation

Acetylation describes a reaction, usually with acetic acid, that introduces an acetyl functional group into an organic compound. ... Acetyl is the radical of acetic acid. ... The N-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free amine group (NH2). ... Alkylation is the transfer of an alkyl group from one molecule to another. ... An alkyl is a univalent radical containing only carbon and hydrogen atoms arranged in a chain. ... Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ... In chemistry a methyl-group is a hydrophobic Alkyl functional group which is derived from methane (CH4). ... Lysine is one of the 20 amino acids normally found in proteins. ... Arginine (symbol Arg or R) is an α-amino acid. ... Biotinylation is the process of adding a Biotin tag to a molecule or surface. ... Lysine is one of the 20 amino acids normally found in proteins. ... Glutamic acid (Glu), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. ... Glycine (Gly, G) is a nonpolar amino acid. ... Tubulin is the protein which makes up microtubules. ... Glycosylation is the process or result of addition of saccharides to proteins and lipids. ... A glycosyl group is a structure obtained by removing the hydroxy group from the hemiacetal function of a monosaccharide and, by extension, of a lower oligosaccharide. ... Asparagine is one of the 20 most common natural amino acids on Earth. ... Hydroxylysine is an amino acid, C6H14N2O3. ... Serine is one of the 20 natural amino acids. ... Threonine is one of the 20 natural amino acids. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (an oligosaccharide). ... Prenylation or isoprenylation is the addition of hydrophobic molecules to a protein to facilitate its attachment to the cell membrane. ... The terpenoids, sometimes referred to as isoprenoids, are a class of naturally occurring chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. ... Acetyl Coenzyme A Acetyl-CoA Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidization of fatty acids, and the oxidation of pyruvate in the citric acid cycle. ... Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule. ... Above is a ball-and-stick model of the inorganic phosphate molecule (HPO42−). Colour coding: P (orange); O (red); H (white). ... Serine is one of the 20 natural amino acids. ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ... Threonine is one of the 20 natural amino acids. ... Histidine is one of the 20 most common natural amino acids present in proteins. ... Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ...

PTMs involving addition of other proteins or peptides

• ISGylation, the covalent linkage to the ISG15 protein (Interferon-Stimulated Gene 15) (2)
• SUMOylation, the covalent linkage to the SUMO protein (Small Ubiquitin-related MOdifier) (1)
• ubiquitination, the covalent linkage to the protein ubiquitin.

Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ... Small Ubiquitin-related Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. ... Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ... Small Ubiquitin-related Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. ... Ubiquitin is a small regulatory protein that is ubiquitous in eukaryotes. ... Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ...

PTMs involving changing the chemical nature of amino acids

• citrullination, or deimination the conversion of arginine to citrulline
• deamidation, the conversion of glutamine to glutamic acid or asparagine to aspartic acid

Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. ... Arginine (symbol Arg or R) is an α-amino acid. ... The chemical compound citrulline is an α-amino acid (AA). ... Deamidation reaction of Asn-Gly (top right) to Asp-Gly (at left) or iso(Asp)-Gly (in green at bottom right). ... Glutamine is one of the 20 amino acids encoded by the standard genetic code. ... Glutamic acid (Glu), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. ... Asparagine is one of the 20 most common natural amino acids on Earth. ... Aspartic acid (Asp), also known as aspartate, the name of its anion, is one of the 20 natural proteinogenic amino acids which are the building blocks of proteins. ...

PTMs involving structural changes

• disulfide bridges, the covalent linkage of two cysteine amino acids
• proteolytic cleavage, cleavage of a protein at a peptide bond

A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ... Cysteine is a naturally occurring amino acid which has a thiol group and is found in most proteins, though only in small quantities. ... Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ...

Case examples

• cleavage and formation of disulfide bridges during the production of insulin
• PTM of histones as regulation of transcription: RNA polymerase control by chromatin structure
• PTM of RNA polymerase II as regulation of transcription: RNA polymerase II

It has been suggested that Oral insulin be merged into this article or section. ... In biology, histones are the chief proteins of chromatin. ... This is an outline of an example mechanism of yeast cells by which chromatin structure and histone posttranslational modification help regulate and record the transcription of genes by RNA polymerase II. This pathway gives examples of regulation at these points of transcription: Pre-initiation (promotion by Bre1, histone modification) Initiation... RNA polymerase II (also called RNAP II and Pol II) transcribes DNA to synthesize precursors of mRNA and most snRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. ...

References

1. Van G. Wilson (Ed.) (2004). Sumoylation: Molecular Biology and Biochemistry. Horizon Bioscience. ISBN 0-9545232-8-8.

2. Malakhova, Oxana A.; Yan, Ming; Malakhov, Michael P.; Yuan, Youzhong; Ritchie, Kenneth J.; Kim, Keun Il; Peterson, Luke F.; Shuai, Ke; and Dong-Er Zhang. (2003). Protein ISGylation modulates the JAK-STAT signaling pathway. Genes & Development 17 (4), 455-460.