A Computational Study of the Mechanism of Succinimide Formation in the Asn-His Sequence: Intramolecular Catalysis by the His Side Chain.

ABSTRACT: The rates of deamidation reactions of asparagine (Asn) residues which occur spontaneously and nonenzymatically in peptides and proteins via the succinimide intermediate are known to be strongly dependent on the nature of the following residue on the carboxyl side (Xxx). The formation of the succinimide intermediate is by far the fastest when Xxx is glycine (Gly), the smallest amino acid residue, while extremely slow when Xxx is bulky such as isoleucine (Ile) and valine (Val). In this respect, it is very interesting to note that the succinimide formation is definitely accelerated when Xxx is histidine (His) despite its large size. In this paper, we computationally show that, in an Asn-His sequence, the His side-chain imidazole group (in the neutral Nε-protonated form) can specifically catal

SUBMITTER: Takahashi O 

PROVIDER: S-EPMC6274526 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature