QM/MM simulations identify the determinants of catalytic activity differences between type II dehydroquinase enzymes.

ABSTRACT: Type II dehydroquinase enzymes (DHQ2), recognized targets for antibiotic drug discovery, show significantly different activities dependent on the species: DHQ2 from Mycobacterium tuberculosis (MtDHQ2) and Helicobacter pylori (HpDHQ2) show a 50-fold difference in catalytic efficiency. Revealing the determinants of this activity difference is important for our understanding of biological catalysis and further offers the potential to contribute to tailoring specificity in drug design. Molecular dynamics simulations using a quantum mechanics/molecular mechanics potential, with correlated ab initio single point corrections, identify and quantify the subtle determinants of the experimentally observed difference in efficiency. The rate-determining step involves the formation of an enolate interme

SUBMITTER: Lence E 

PROVIDER: S-EPMC6011038 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature