Atomic model of a cell-wall cross-linking enzyme in complex with an intact bacterial peptidoglycan - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of the American Chemical Society Année : 2014

Atomic model of a cell-wall cross-linking enzyme in complex with an intact bacterial peptidoglycan

Résumé

The maintenance of bacterial cell shape and integrity is largely attributed to peptidoglycan, a highly cross-linked biopolymer. The transpeptidases that perform this cross-linking are important targets for antibiotics. Despite this biomedical importance to date no structure of a protein in complex with an intact bacterial peptidoglycan has been re-solved, primarily due to the large size and flexibility of peptidoglycan sacculi. Here we use solid-state NMR spec-troscopy to derive for the first time an atomic model of an L,D-transpeptidase from Bacillussubtilis bound to its natural substrate, the intact B. subtilis peptidoglycan. Importantly, the model obtained from protein chemical shift perturbation data shows that both domains – the catalytic domain as well as the proposed peptidoglycan recognition domain – are important for the interaction and reveals a novel binding motif that involves residues outside of the classical enzymatic pocket. Experiments on mutants and truncated protein constructs independently confirm the binding site and the impli-cation of both domains. Through measurements of dipolar-coupling derived order parameters of bond motion we show that protein binding reduces the flexibility of peptidoglycan. This first report of an atomic model of a protein-peptidogly -can complex paves the way for the design of new antibiotic drugs targeting L,D-transpeptidases. The strategy devel-oped here can be extended to the study of a large variety of enzymes involved in peptidoglycan morphogenesis.
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Dates et versions

hal-01093364 , version 1 (18-12-2014)

Identifiants

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Paul Schanda, Sébastien Triboulet, Cédric Laguri, Catherine M Bougault, Isabel Ayala, et al.. Atomic model of a cell-wall cross-linking enzyme in complex with an intact bacterial peptidoglycan. Journal of the American Chemical Society, 2014, 136 (51), pp.10. ⟨10.1021/ja5105987⟩. ⟨hal-01093364⟩
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