Sequence and structure determinants of the nonenzymatic deamidation of asparagine and glutamine residues in proteins.
The rates of deamidation of Asn and Gln residues in peptides and proteins depend upon both the identity of other nearby amino acid residues, some of which can catalyze the deamidation reaction of the Asn and Gln side chains, and upon polypeptide conformation. Proximal amino acids can be contiguous in sequence or brought close to Asn or Gln side chains by higher order structure of the protein. Local polypeptide conformation can stabilize the oxyanion transition state of the deamidation reaction and also enable deamidation through the beta-aspartyl shift mechanism. In this paper, the environments of Asn and Gln residues in known protein structures are examined to determine the configuration and identity of groups which participate in deamidation reactions. Sequence information is also analyzed and shown to support evolutionary selection against the occurrence of certain potentially catalytic amino acids adjacent to Asn and Gln in proteins. This negative selection supports a functional role for deamidation in those non-mutant proteins in which it occurs.
Wright
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Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond 23298-0614.
D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry* / Q000502:physiology; D003198:Computer Simulation; D003574:Cytochrome c Group / Q000737:chemistry; D005973:Glutamine / Q000737:chemistry* / Q000502:physiology; D006448:Hemoglobin J / Q000737:chemistry; D006455:Hemoglobins, Abnormal / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D014305:Triose-Phosphate Isomerase / Q000737:chemistry
D003574:Cytochrome c Group; D006455:Hemoglobins, Abnormal; D007328:Insulin; C069973:hemoglobin Singapore; D005973:Glutamine; D006448:Hemoglobin J; C049101:hemoglobin J Providence; D001216:Asparagine; D012259:Ribonuclease, Pancreatic; D014305:Triose-Phosphate Isomerase