Novel fragments of clavulanate observed in the structure of the class A beta-lactamase from Bacillus licheniformis BS3

作者：Power Pablo; Mercuri Paola; Herman Raphael; Kerff Frederic; Gutkind Gabriel; Dive Georges; Galleni Moreno; Charlier Paulette; Sauvage Eric^*

来源：Journal of Antimicrobial Chemotherapy, 2012, 67(10): 2379-2387.

DOI：10.1093/jac/dks231

• bacterial resistance
• clavulanate
• -lactamase inactivation

Our aim was to unravel the inactivation pathway of the class A -lactamase produced by Bacillus licheniformis BS3 (BS3) by clavulanate. %26lt;br%26gt;The interaction between clavulanate and BS3 was studied by X-ray crystallography, pre-steady-state kinetics and mass spectrometry. %26lt;br%26gt;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 -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 -lactamase (Mtu). %26lt;br%26gt;This work provides a comprehensive clavulanate hydrolysis pathway accounting for the observed acyl-enzyme structures of class A -lactamase/clavulanate adducts.

• 出版日期2012-10