Conformational Intermediate That Controls KPC-2 Catalysis and Beta-Lactam Drug Resistance.

ABSTRACT: The KPC-2 carbapenemase enzyme is responsible for drug resistance in the majority of carbapenem-resistant gram-negative bacterial infections in the United States. A better understanding of what permits KPC-2 to hydrolyze carbapenem antibiotics and how this might be inhibited is thus of fundamental interest and great practical importance to development of better anti-infectives. By correlating molecular dynamics simulations with experimental enzyme kinetics, we have identified conformational changes that control KPC-2's ability to hydrolyze carbapenem antibiotics. Related beta-lactamase enzymes can interconvert between catalytically permissive and catalytically nonpermissive forms of an acylenzyme intermediate critical to drug hydrolysis. Using molecular dynamics simulations, we identify a

SUBMITTER: Cortina GA 

PROVIDER: S-EPMC6324736 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature