Download MendeleyNovel Fragments of Clavulanate Observed in the Structure of the Class a Beta-Lactamase from Bacillus Licheniformis Bs3.
Power, P., Mercuri, P., Herman, R., Kerff, F., Gutkind, G., Dive, G., Galleni, M., Charlier, P., Sauvage, E.(2012) J Antimicrob Chemother 67: 2379
- PubMed: 22773738
- DOI: https://doi.org/10.1093/jac/dks231
- Primary Citation of Related Structures:
2Y91 - PubMed Abstract:
Our aim was to unravel the inactivation pathway of the class A ¦Â-lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. The analysis of the X-ray structure of the complex yielded by the reaction between clavulanate and BS3 indicates that the transient inactivated form, namely the cis-trans enamine complex, is hydrolysed to an ethane-imine ester covalently linked to the active site serine and a pentan-3-one-5-ol acid. It is the first time that this mechanism has been observed in an inactivated ¦Â-lactamase. Furthermore, the ionic interactions made by the carboxylic group of pentan-3-one-5-ol may provide an understanding of the decarboxylation process of the trans-enamine observed in the non-productive complex observed for the interaction between clavulanate and SHV-1 and Mycobacterium tuberculosis ¦Â-lactamase (Mtu). This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A ¦Â-lactamase/clavulanate adducts.
Organizational Affiliation:
Laboratorio de Resistencia Bacteriana, Facultad de Farmacia y Bioqu¨ªmica, Universidad de Buenos Aires, Junin 956, (1113) Buenos Aires, Argentina.
