1M2X

Crystal Structure of the metallo-beta-lactamase BlaB of Chryseobacterium meningosepticum in complex with the inhibitor D-captopril

Summary for 1M2X

• Entry DOI: 10.2210/pdb1m2x/pdb
• Descriptor: class B carbapenemase BlaB-1, SODIUM ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: alpha-beta/beta-alpha fold., hydrolase
• Biological source: Elizabethkingia meningoseptica
• Total number of polymer chains: 4
• Total formula weight: 103535.45

Authors

Garcia-Saez, I.,Dideberg, O. (deposition date: 2002-06-26, release date: 2003-07-29, Last modification date: 2024-02-14)

Primary citation

Garcia-Saez, I.,Hopkins, J.,Papamicael, C.,Franceschini, N.,Amicosante, G.,Rossolini, G.M.,Galleni, M.,Frere, J.M.,Dideberg, O.
The 1.5 A structure of Chryseobacterium meningosepticum Zn-beta-lactamase in complex with the inhibitor, D-captopril
J.Biol.Chem., 278:23868-23873, 2003

PubMed Abstract: The crystal structure of the class-B beta-lactamase, BlaB, from the pathogenic bacterium, Chryseobacterium meningosepticum, in complex with the inhibitor, d-captopril, has been solved at 1.5-A resolution. The enzyme has the typical alphabeta/betaalpha metallo-beta-lactamase fold and the characteristic two metal binding sites of members of the subclass B1, in which two Zn2+ ions were identified. d-Captopril, a diastereoisomer of the commercial drug, captopril, acts as an inhibitor by displacing the catalytic hydroxyl ion required for antibiotic hydrolysis and intercalating its sulfhydryl group between the two Zn2+ ions. Interestingly, d-captopril is located on one side of the active site cleft. The x-ray structure of the complex of the closely related enzyme, IMP-1, with a mercaptocarboxylate inhibitor, which also contains a sulfhydryl group bound to the two Zn2+ ions, shows the ligand to be located on the opposite side of the active site cleft. A molecule generated by fusion of these two inhibitors would cover the entire cleft, suggesting an interesting approach to the design of highly specific inhibitors.

PubMed: 12684522
DOI: 10.1074/jbc.M301062200

Experimental method

X-RAY DIFFRACTION (1.5 Å)