Kinetic characterization of GES-22 beta-lactamase harboring the M169L clinical mutation
Citation
Saral, A., Leonard, D. A., Duzgun, A. O., Cicek, A. C., June, C. M., & Sandalli, C. (2016). Kinetic characterization of GES-22 β-lactamase harboring the M169L clinical mutation. The Journal of antibiotics, 69(12), 858–862. https://doi.org/10.1038/ja.2016.48Abstract
The class A p-lactamase GES-22 has been identified in Acinetobacter baumannii isolates in Turkey, and subsequently shown to differ from GES-11 by a single substitution (M169L). Because M169 is part of the omega loop, a structure that is known to have major effects on substrate selectivity in class A beta-lactamases, we expressed, purified and kinetically characterized this novel variant. Our results show that compared with GES-11(6xHis), GES-22(6xHis) displays more efficient hydrolysis of penicillins, and aztreonam, but a loss of efficiency against ceftazidime. in addition, the M169L substitution confers on GES-22 more efficient hydrolysis of the mechanistic inhibitors clavulanic acid and sulbactam. These effects are highly similar to other mutations at the homologous position in other class A beta-lactamases, suggesting that this methionine has a key structural role in aligning active site residues and in substrate selectivity across the class.
