A minimalistic approach to identify substrate binding features in B1 Metallo-beta-lactamases

A.A. Poeylaut-Palena , P.E. Tomatis , A.I. Karsisiotis (1) , Christian Damblon (1) , E.G. Mata , A.J. Vila

1 CBM - Centre de biophysique moléculaire

The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal P-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-p-lactamase Bell. None of them was hydrolyzed by the enzyme. While the azetidinone was not able to bind Bell, aztreonam was shown to bind in a nonproductive mode. These results provide an explanation for the unability of Metallo-beta-lactamases to inactive monobactams and give some clues for inhibitor design.

Mots clés: etallo-beta-lactamases; inhibitor design; ligand binding; monocyclic beta-lactams

A.A. Poeylaut-Palena, P.E. Tomatis, A.I. Karsisiotis, Christian Damblon, E.G. Mata, et al.. A minimalistic approach to identify substrate binding features in B1 Metallo-beta-lactamases. Bioorganic and Medicinal Chemistry Letters, 2007, 17, pp.5171-5174. ⟨hal-00512423⟩