Structural highlights
FunctionPublication Abstract from PubMedOBJECTIVES: Our aim was to unravel the inactivation pathway of the class A beta-lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. METHODS: The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. RESULTS: 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 beta-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 beta-lactamase (Mtu). CONCLUSIONS: This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A beta-lactamase/clavulanate adducts. Novel 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 J Antimicrob Chemother. 2012 Oct;67(10):2379-87. Epub 2012 Jul 6. PMID:22773738[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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