A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1–BLIP complex - Archive ouverte HAL Access content directly
Journal Articles Nature Structural Biology Year : 1996

A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1–BLIP complex

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Abstract

The structure of TEM-1 beta-lactamase complex with the inhibitor BLIP has been determined at 1.7 angstrom resolution. The two tandemly repeated domains of BLIP form a polar, concave surface that docks onto a predominantly polar, convex protrusion on the enzyme. The ability of BLIP to adapt to a variety of class A beta-lactamases is most likely due to an observed flexibility between the two domains of the inhibitor and to an extensive layer of water molecules entrapped between the enzyme and inhibitor. A beta-hairpin loop from domain 1 of BLIP is inserted into the active site of the beta-lactamase. The carboxylate of Asp 49 forms hydrogen bonds to four conserved, catalytic residues in the beta-lactamase, thereby mimicking the position of the penicillin G carboxylate observed in the acyl-enzyme complex of TEM-1 with substrate. This beta-hairpin may serve as a template with which to create a new family of peptide-analogue beta-lactamase inhibitors.

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pasteur-03136592 , version 1 (09-02-2021)

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Natalie C.J. Strynadka, Susan E. Jensen, Pedro M. Alzari, Michael N.G. James. A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1–BLIP complex. Nature Structural Biology, 1996, 3 (3), pp.290-297. ⟨10.1038/nsb0396-290⟩. ⟨pasteur-03136592⟩

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