 |
Journal articles
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.
https://hal-pasteur.archives-ouvertes.fr/pasteur-03136592
Contributor : Marie de TARRAGON Connect in order to contact the contributor
Submitted on : Tuesday, February 9, 2021 - 6:21:51 PM
Last modification on : Thursday, April 7, 2022 - 10:10:29 AM
Contributor : Marie de TARRAGON Connect in order to contact the contributor
Submitted on : Tuesday, February 9, 2021 - 6:21:51 PM
Last modification on : Thursday, April 7, 2022 - 10:10:29 AM
Links full text
