Non-Hydrolytic β-Lactam Antibiotic Fragmentation by l,d-Transpeptidases and Serine β-Lactamase Cysteine Variants.

ABSTRACT: Enzymes often use nucleophilic serine, threonine, and cysteine residues to achieve the same type of reaction; the underlying reasons for this are not understood. While bacterial d,d-transpeptidases (penicillin-binding proteins) employ a nucleophilic serine, l,d-transpeptidases use a nucleophilic cysteine. The covalent complexes formed by l,d-transpeptidases with some β-lactam antibiotics undergo non-hydrolytic fragmentation. This is not usually observed for penicillin-binding proteins, or for the related serine β-lactamases. Replacement of the nucleophilic serine of serine β-lactamases with cysteine yields enzymes which fragment β-lactams via a similar mechanism as the l,d-transpeptidases, implying the different reaction outcomes are principally due to the formation of thioester versus est

SUBMITTER: Lohans CT 

PROVIDER: S-EPMC6391942 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature