Biochemical and crystallographic studies of L,D-transpeptidase 2 from Mycobacterium tuberculosis with its natural monomer substrate.

ABSTRACT: The essential L,D-transpeptidase of Mycobacterium tuberculosis (Ldt_Mt2) catalyses the formation of 3 → 3 cross-links in cell wall peptidoglycan and is a target for development of antituberculosis therapeutics. Efforts to inhibit Ldt_Mt2 have been hampered by lack of knowledge of how it binds its substrate. To address this gap, we optimised the isolation of natural disaccharide tetrapeptide monomers from the Corynebacterium jeikeium bacterial cell wall through overproduction of the peptidoglycan sacculus. The tetrapeptides were used in binding / turnover assays and biophysical studies on Ldt_Mt2. We determined a crystal structure of wild-type Ldt_Mt2 reacted with its natural substrate, the tetrapeptide monomer of the peptidoglycan layer. This structu

SUBMITTER: de Munnik M 

PROVIDER: S-EPMC11410929 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature