Abstract
The structure of TEM-1 β-lactamase complexed with the inhibitor BLIP has been determined at 1.7 Å 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 β-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 β-hairpin loop from domain 1 of BLIP is inserted into the active site of the β-lactamase. The carboxylate of Asp 49 forms hydrogen bonds to four conserved, catalytic residues in the β-lactamase, thereby mimicking the position of the penicillin G carboxylate observed in the acyl–enzyme complex of TEM-1 with substrate. This β-hairpin may serve as a template with which to create a new family of peptide-analogue β-lactamase inhibitors.
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Strynadka, N., Jensen, S., Alzari, P. et al. A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1–BLIP complex. Nat Struct Mol Biol 3, 290–297 (1996). https://doi.org/10.1038/nsb0396-290
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DOI: https://doi.org/10.1038/nsb0396-290
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