Computational design of catalytic dyads and oxyanion holes for ester hydrolysis.

ABSTRACT: Nucleophilic catalysis is a general strategy for accelerating ester and amide hydrolysis. In natural active sites, nucleophilic elements such as catalytic dyads and triads are usually paired with oxyanion holes for substrate activation, but it is difficult to parse out the independent contributions of these elements or to understand how they emerged in the course of evolution. Here we explore the minimal requirements for esterase activity by computationally designing artificial catalysts using catalytic dyads and oxyanion holes. We found much higher success rates using designed oxyanion holes formed by backbone NH groups rather than by side chains or bridging water molecules and obtained four active designs in different scaffolds by combining this motif with a Cys-His dyad. Following activ

SUBMITTER: Richter F 

PROVIDER: S-EPMC4104585 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature