Kinetic characterization of GES-22 beta-lactamase harboring the M169L clinical mutation

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Saral A., Leonard D. A., Duzgun A. O., Cicek A., June C. M., SANDALLI C.

JOURNAL OF ANTIBIOTICS, vol.69, no.12, pp.858-862, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 69 Issue: 12
  • Publication Date: 2016
  • Doi Number: 10.1038/ja.2016.48
  • Journal Name: JOURNAL OF ANTIBIOTICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.858-862
  • Recep Tayyip Erdoğan University Affiliated: Yes

Abstract

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.