1BLC

INHIBITION OF BETA-LACTAMASE BY CLAVULANATE: TRAPPED INTERMEDIATES IN CRYOCRYSTALLOGRAPHIC STUDIES

Summary for 1BLC

• Entry DOI: 10.2210/pdb1blc/pdb
• Descriptor: BETA-LACTAMASE, SULFATE ION, N-(1-CARBOXY-2-HYDROXY-4-OXO-BUTYL)-N-(3-OXO-CISPROPENYL)AMINE, ... (5 entities in total)
• Functional Keywords: hydrolase(acting in cyclic amides)
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 29297.62

Authors

Chen, C.C.H.,Herzberg, O. (deposition date: 1993-09-27, release date: 1994-01-31, Last modification date: 2024-10-16)

Primary citation

Chen, C.C.,Herzberg, O.
Inhibition of beta-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies.
J.Mol.Biol., 224:1103-1113, 1992

PubMed Abstract: Crystallographic studies of the complex between beta-lactamase and clavulanate reveal a structure of two acyl-enzymes with covalent bonds at the active site Ser70, representing two different stages of inhibitor degradation alternately occupying the active site. Models that are consistent with biochemical data are derived from the electron density map and refined at 2.2 A resolution: cis enamine, in which the carboxylate group of the clavulanate molecule makes a salt bridge with Lys234 of beta-lactamase; decarboxylated trans enamine, which is oriented away from Lys234. For both acyl-enzymes, the carbonyl oxygen atom of the ester group occupies the oxyanion hole in a manner similar to that found in inhibitor binding to serine proteases. Whereas the oxygen atom in the trans product is optimally positioned in the oxyanion hole, that of the cis product clashes with the main-chain nitrogen atom of Ser70 and the beta-carbon atom of the adjacent Ala69. In contrast to cis to trans isomerization in solution that relieves the steric strain inherent in a cis double bond, at the enzyme-inhibitor interface two additional factors play an important role. The salt bridge enhances the stability of the cis product, while the steric strain introduced by the short contacts with the protein reduces its stability.

PubMed: 1569569
DOI: 10.1016/0022-2836(92)90472-V

Experimental method

X-RAY DIFFRACTION (2.2 Å)