Mechanistic Basis of OXA-48-like β-Lactamases' Hydrolysis of Carbapenems.

ABSTRACT: Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are an important source of resistance to these last resort β-lactam antibiotics. OXA-48 is a member of a group of CHDLs named OXA-48-like enzymes. On the basis of sequence similarity, OXA-163 can be classified as an OXA-48-like enzyme, but it has altered substrate specificity. Compared to OXA-48, it shows impaired activity for carbapenems but displays an enhanced hydrolysis of oxyimino-cephalosporins. Here, we address the mechanistic and structural basis for carbapenem hydrolysis by OXA-48-like enzymes. Pre-steady-state kinetic analysis indicates that the rate-limiting step for OXA-48 and OXA-163 hydrolysis of carbapenems is deacylation and that the greatly reduced carbapenemase activity of OXA-163 compared to that of OXA-48 is due entire

SUBMITTER: Stojanoski V 

PROVIDER: S-EPMC8571991 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature