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

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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Submitted on : Tuesday, February 9, 2021 - 6:21:51 PM
Last modification on : Saturday, April 3, 2021 - 3:19:17 AM

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Natalie C.J. Strynadka, Susan Jensen, Pedro 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, Nature Publishing Group, 1996, 3 (3), pp.290-297. ⟨10.1038/nsb0396-290⟩. ⟨pasteur-03136592⟩

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