Computational Studies on the Nonenzymatic Deamidation Mechanisms of Glutamine Residues.

ABSTRACT: The nonenzymatic deamidation reactions of asparagine (Asn) and glutamine (Gln) residues in proteins are associated with protein turnover and age-related diseases. The reactions are also believed to provide a molecular clock for biological processes. Although Gln deamidation is assumed to occur through the glutarimide intermediate, the mechanisms for this are unclear because under normal physiological conditions, Gln deamidation occurs relatively less frequently and at a lower rate than Asn deamidation. We investigate the mechanisms underlying glutarimide formation from Gln residues, which proceeds in two steps (cyclization and deammoniation) catalyzed by phosphate and carbonate. We also compare these reactions with noncatalytic mechanisms and water-catalyzed mechanisms. The calculations we

SUBMITTER: Kato K 

PROVIDER: S-EPMC6648516 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature