The Role of the ?-Loop in Regulation of the Catalytic Activity of TEM-Type ?-Lactamases.

ABSTRACT: Bacterial resistance to ?-lactams, the most commonly used class of antibiotics, poses a global challenge. This resistance is caused by the production of bacterial enzymes that are termed ?-lactamases (?Ls). The evolution of serine-class A ?-lactamases from penicillin-binding proteins (PBPs) is related to the formation of the ?-loop at the entrance to the enzyme's active site. In this loop, the Glu166 residue plays a key role in the two-step catalytic cycle of hydrolysis. This residue in TEM-type ?-lactamases, together with Asn170, is involved in the formation of a hydrogen bonding network with a water molecule, leading to the deacylation of the acyl-enzyme complex and the hydrolysis of the ?-lactam ring of the antibiotic. The activity exhibited by the ?-loop is attributed to the positioning of its N-terminal residues near the catalytically important residues of the active site. The structure of the ?-loop of TEM-type ?-lactamases is characterized by low mutability, a stable topology, and structural flexibility. All of the revealed features of the ?-loop, as well as the mechanisms related to its involvement in catalysis, make it a potential target for novel allosteric inhibitors of ?-lactamases.

SUBMITTER: Egorov A 

PROVIDER: S-EPMC6995641 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature