Deamidation

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Deamidation reaction of Asn-Gly (top right) to Asp-Gly (at left) or iso(Asp)-Gly (in green at bottom right).


Deamidation is a chemical reaction in which an amide functional group is removed from an organic compound. In biochemistry, the reaction is important in the degradation of proteins because it damages the amide-containing side chains of the amino acids asparagine and glutamine.

In the biochemical deamidation reaction, the side chain of an asparagine attacks the following peptide group (in black at top right of Figure), forming a symmetric succinimide intermediate (in red). The symmetry of the intermediate results in two products of its hydrolysis, either aspartate (in black at left) or in isoaspartate, which is a beta amino acid (in green at bottom right). This process is considered a deamidation because the amide in the asparagine side chain is replaced by a carboxylate group. However, a similar reaction can occur in aspartate side chains, yielding a partial conversion to isoaspartate.

Kinetics of deamidation

Deamidation reactions have been conjectured to be one of the factors that limit the useful lifetime of proteins.

Deamidation proceeds much more quickly if the susceptible amino acid is followed by a small, flexible residue such as glycine whose low steric hindrance leaves the peptide group open for attack. Deamidation reactions also proceed much more quickly at elevated pH (>10) and temperature.

References

  • Clarke S. (1987) "Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins", Int. J., Peptide Protein Res., 30, 808-821.
  • Stephenson RC and Clarke S. (1989) "Succinimide Formation from Aspartyl and Asparaginyl Peptides as a Model for the Spontaneous Degradation of Proteins", J. Biol. Chem., 264, 6164-6170.

See also



Robinson NE, Robinson AB. Molecular Clocks: Deamidation of Asparaginyl and Glutaminyl Residues in Peptides and Proteins. Althouse Press: Cave Junction, Ore. OCLC 56978028
amide is one of two kinds of compounds:
  • the organic functional group characterized by a carbonyl group (C=O) linked to a nitrogen atom (N), or a compound that contains this functional group (pictured to the right); or
  • a particular kind of nitrogen anion.

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In organic chemistry, functional groups (or moieties) are specific groups of atoms within molecules, that are responsible for the characteristic chemical reactions of those molecules.
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organic compounds]] An organic compound is any member of a large class of chemical compounds whose molecules contain carbon; for historical reasons discussed below, a few types of compounds such as carbonates, carbon oxides and cyanides, as well as elemental carbon are
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Biochemistry is the study of the chemical processes in living organisms.[1] The word "biochemistry" comes from the Greek word βιοχημεία biochēmeia, which means "the chemistry of life.
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Proteins are large organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues.
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side chain in organic chemistry and biochemistry is a part of a molecule that is attached to a core structure. An R group is a generic label for a side chain which can be anything; however, it is typically stable and covalently linked to the adjoining atom.
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amino acid is a molecule that contains both amine and carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent.
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For other articles using the abbreviation or acronym asn see ASN.


Asparagine (abbreviated as Asn or N; Asx or B
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Glutamine (abbreviated as Gln or Q; Glx or Z represents either glutamine or glutamic acid) is one of the 20 amino acids encoded by the standard genetic code.
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Succinimide is a cyclic imide with the formula C4H5NO2. It appears as a white or colorless crystalline solid, and has a faint odor of sweat. It is used in a variety of organic synthesis, as well as in some industrial silver plating processes.
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Aspartic acid or aspartate (abbreviated as Asp or D; Asx or B represent either aspartic acid or asparagine)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CO2H.
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isoaspartate group is a functional group in biochemistry [1] [2]. Its formation is a chemical reaction in which the side chain of an asparagine or aspartic acid residue attacks the following peptide group (in black at top right of Figure 1), forming a
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β-peptides consist of β amino acids, which have their amino group bonded to the β carbon rather than the α carbon as in the 20 standard biological amino acids.
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Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -C(=O)OH, usually written -COOH or -CO2H. [1] Carboxylic acids are Bronsted acids — they are proton donors.
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Glycine (abbreviated as Gly or G)[1] is the organic compound with the formula HO2CCH2NH2.
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Steric effects arise from the fact that each atom within a molecule occupies a certain amount of space. If atoms are brought too close together, there is an associated cost in energy due to overlapping electron clouds (Pauli or Born repulsion), and this may affect the molecule's
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A peptide bond is a chemical bond that is formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O).
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    pH is a measure of the acidity or alkalinity of a solution. Aqueous solutions at 25 ℃ with a pH less than seven are considered acidic, while those with a pH greater than seven are considered basic (alkaline). The pH of 7.
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    trillion fold).]]

    Temperature is a physical property of a system that underlies the common notions of hot and cold; something that is hotter generally has the greater temperature. Temperature is one of the principal parameters of thermodynamics.
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    A peptide bond is a chemical bond that is formed between two molecules when the carboxyl group of one molecule reacts with the amino group of the other molecule, releasing a molecule of water (H2O).
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    Post-translational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins. A protein (also called a polypeptide) is a chain of amino acids.
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    primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms (including stereochemistry). For a typical unbranched, un-crosslinked biopolymer (such as a molecule of DNA, RNA or typical intracellular
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    Post-translational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins. A protein (also called a polypeptide) is a chain of amino acids.
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    Protein biosynthesis (synthesis) is the process in which cells build proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription which are then used for translation.
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    The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) refers to the end of a protein or polypeptide terminated by an amino acid with a free amine group (-NH2).
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    Acetylation (or in IUPAC nomenclature ethanoylation) describes a reaction that introduces an acetyl functional group into an organic compound. Deacetylation is the removal of the acetyl group.
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    The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal end, or COOH-terminus) of a protein or polypeptide is the end of the amino acid chain terminated by a free carboxyl group (-COOH).
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    amide is one of two kinds of compounds:
    • the organic functional group characterized by a carbonyl group (C=O) linked to a nitrogen atom (N), or a compound that contains this functional group (pictured to the right); or
    • a particular kind of nitrogen anion.

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    Lysine (abbreviated as Lys or K)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)(CH2)4NH2.
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    Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. This term is commonly used in chemistry, biochemistry, and the biological sciences.
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