Kinetic characterization of GES-22 β-lactamase harboring the M169L clinical mutation
Journal of Antibiotics, cilt.69, sa.12, ss.858-862, 2016 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 69 Sayı: 12
- Basım Tarihi: 2016
- Doi Numarası: 10.1038/ja.2016.48
- Dergi Adı: Journal of Antibiotics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.858-862
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- İstanbul Medipol Üniversitesi Adresli: Evet
Özet
The class A β-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 β-lactamases, we expressed, purified and kinetically characterized this novel variant. Our results show that compared with GES-116×His, GES-226×His 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 β-lactamases, suggesting that this methionine has a key structural role in aligning active site residues and in substrate selectivity across the class.