24 research outputs found
Flexible matching of test ligands to a 3D pharmacophore using a molecular superposition force field: Comparison of predicted and experimental conformations of inhibitors of three enzymes
A low energy short hydrogen bond in very high resolution structures of protein receptor-phosphate complexes
Structure of and kinetic channelling in bifunctional dihydrofolate reductase–thymidylate synthase
Alternating arginine-modulated substrate specificity in an engineered tyrosine aminotransferase
A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1–BLIP complex
International audienceThe 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