On the Origin of Substrate Specificity of Enzymes from the Amidohydrolase Superfamily.

ABSTRACT: The sequencing of numerous genomes has led to the identification of open reading frames for millions of enzymes, many of which use unknown substrates. Hence, the identification of both primary and promiscuous activities remains a major challenge for enzyme research. Here, we identified the mechanistic basis of substrate specificity for members of the amidohydrolase superfamily (AHS). Comprehensive analyses of two AHS classes revealed that catalysis proceeds either via 1,4 or 1,6 nucleophilic conjugate addition mediated by a glutamine that is located at two different positions within the active site thereby shaping substrate scope in these enzymes. These different enzymatic properties result in an inverted enantioselectivity for fleeting chiral intermediates, which are transient chiral spec

SUBMITTER: Drexler L 

PROVIDER: S-EPMC12828455 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature