Mutations Utilize Dynamic Allostery to Confer Resistance in TEM-1 β-lactamase.

ABSTRACT: β-lactamases are enzymes produced by bacteria to hydrolyze β-lactam antibiotics as a common mechanism of resistance. Evolution in such enzymes has been rendering a wide variety of antibiotics impotent, therefore posing a major threat. Clinical and in vitro studies of evolution in TEM-1 β-lactamase have revealed a large number of single point mutations that are responsible for driving resistance to antibiotics and/or inhibitors. The distal locations of these mutations from the active sites suggest that these allosterically modulate the antibiotic resistance. We investigated the effects of resistance driver mutations on the conformational dynamics of the enzyme to provide insights about the mechanism of their long-distance interactions. Through all-atom molecular dynamics (MD) simulations, w

SUBMITTER: Modi T 

PROVIDER: S-EPMC6321620 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature