Molecular Bases of the Membrane Association Mechanism Potentiating Antibiotic Resistance by New Delhi Metallo-β-lactamase 1.

ABSTRACT: Resistance to last-resort carbapenem antibiotics is an increasing threat to human health, as it critically limits therapeutic options. Metallo-β-lactamases (MBLs) are the largest family of carbapenemases, enzymes that inactivate these drugs. Among MBLs, New Delhi metallo-β-lactamase 1 (NDM-1) has experienced the fastest and largest worldwide dissemination. This success has been attributed to the fact that NDM-1 is a lipidated protein anchored to the outer membrane of bacteria, while all other MBLs are soluble periplasmic enzymes. By means of a combined experimental and computational approach, we show that NDM-1 interacts with the surface of bacterial membranes in a stable, defined conformation, in which the active site is not occluded by the bilayer. Although the lipidation is required for

SUBMITTER: Prunotto A 

PROVIDER: S-EPMC9062785 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature