Penicillin-binding proteins were long considered as the only
peptidoglycan cross-linking
enzymes and one of the main targets of β-
lactam antibiotics. A new class of
transpeptidases, the L,D-
transpeptidases, has emerged in the last decade. In most Gram-negative and Gram-positive bacteria, these
enzymes generally have nonessential roles in
peptidoglycan synthesis. In some clostridiae and mycobacteria, such as Mycobacterium tuberculosis, they are nevertheless responsible for the major
peptidoglycan cross-linking pathway. L,D-
Transpeptidases are thus considered as appealing new targets for the development of innovative therapeutic approaches.
Carbapenems are currently investigated in this perspective as they are active on extensively
drug-resistant M.
tuberculosis and represent the only β-
lactam class inhibiting L,D-
transpeptidases. The molecular basis of the
enzyme selectivity for
carbapenems nevertheless remains an open question. Here we present the backbone and side-chain (1)H, (13)C, (15)N NMR assignments of the catalytic domain of Enterococcus faecium L,D-
transpeptidase before and after acylation with the
carbapenem ertapenem, as a prerequisite for further structural and functional studies.