The 1.5-Å structure of $Chryseobacterium\ meningosepticum$ zinc β-lactamase in complex with the inhibitor, D-Captopril - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2003

The 1.5-Å structure of $Chryseobacterium\ meningosepticum$ zinc β-lactamase in complex with the inhibitor, D-Captopril

Résumé

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-Å resolution. The enzyme has the typical $\alpha\beta$/$\beta\alpha$ metallo-$\beta$-lactamase fold and the characteristic two metal binding sites of members of the subclass B1, in which two Zn$^{2+}$ 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 Zn$^{2+}$ 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 Zn$^{2+}$ 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.

Domaines

Chimie organique
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Dates et versions

hal-03856326 , version 1 (16-11-2022)

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Isabel García-Sáez, Julie Hopkins, Cyril Papamicaël, Nicola Franceschini, Gianfranco Amicosante, et al.. The 1.5-Å structure of $Chryseobacterium\ meningosepticum$ zinc β-lactamase in complex with the inhibitor, D-Captopril. Journal of Biological Chemistry, 2003, 278, pp.23868 - 23873. ⟨10.1074/jbc.m301062200⟩. ⟨hal-03856326⟩
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