title: Chemical shift perturbations induced by the acylation of Enterococcus faecium L,D-transpeptidase catalytic cysteine with ertapenem.
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.
authors.affiliation: Institut de Biologie Structurale Jean-Pierre Ebel, CEA, 41 rue Jules Horowitz, 38027, Grenoble, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Lecoq
authors.forename: Catherine
authors.initials: C
authors.lastname: Bougault
authors.forename: Sébastien
authors.initials: S
authors.lastname: Triboulet
authors.forename: Vincent
authors.initials: V
authors.lastname: Dubée
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Hugonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Arthur
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Simorre
mesh_terms: D000215:Acylation / Q000187:drug effects; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D003545:Cysteine / Q000378:metabolism*; D016984:Enterococcus faecium / Q000201:enzymology*; D000077727:Ertapenem; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010458:Peptidyl Transferases / Q000737:chemistry* / Q000378:metabolism*; D047090:beta-Lactams / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D047090:beta-Lactams; D010458:Peptidyl Transferases; D000077727:Ertapenem; D003545:Cysteine