Prediction of the Closed Conformation and Insights into the Mechanism of the Membrane Enzyme LpxR.

ABSTRACT: Covalent modification of outer membrane lipids of Gram-negative bacteria can impact the ability of the bacterium to develop resistance to antibiotics as well as modulating the immune response of the host. The enzyme LpxR from Salmonella typhimurium is known to deacylate lipopolysaccharide molecules of the outer membrane; however, the mechanism of action is unknown. Here, we employ molecular dynamics and Monte Carlo simulations to study the conformational dynamics and substrate binding of LpxR in representative outer membrane models as well as detergent micelles. We examine the roles of conserved residues and provide an understanding of how LpxR binds its substrate. Our simulations predict that the catalytic H122 must be Nε-protonated for a single water molecule to occupy the space between

SUBMITTER: Smeddle GM 

PROVIDER: S-EPMC6260217 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature