Chemical shift perturbations induced by the acylation of Enterococcus faecium L,D-transpeptidase catalytic cysteine with ertapenem

Biomol NMR Assign. 2014 Oct;8(2):339-43. doi: 10.1007/s12104-013-9513-3. Epub 2013 Aug 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation / drug effects
  • Amino Acid Sequence
  • Catalytic Domain
  • Cysteine / metabolism*
  • Enterococcus faecium / enzymology*
  • Ertapenem
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular*
  • Peptidyl Transferases / chemistry*
  • Peptidyl Transferases / metabolism*
  • beta-Lactams / metabolism*
  • beta-Lactams / pharmacology

Substances

  • beta-Lactams
  • Peptidyl Transferases
  • Ertapenem
  • Cysteine