3V3S

Crystal structure of GES-18

3V3S の概要

• エントリーDOI: 10.2210/pdb3v3s/pdb
• 関連するPDBエントリー: 2QPN
• 分子名称: Extended spectrum beta-lactamase GES-18 (2 entities in total)
• 機能のキーワード: beta lactamase fold, hydrolase, beta lactams
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62472.98

構造登録者

Delbruck, H.,Hoffmann, K.M.V.,Bebrone, C. (登録日: 2011-12-14, 公開日: 2012-11-28, 最終更新日: 2024-11-06)

主引用文献

Bebrone, C.,Bogaerts, P.,Delbruck, H.,Bennink, S.,Kupper, M.B.,Rezende de Castro, R.,Glupczynski, Y.,Hoffmann, K.M.
GES-18, a new carbapenem-hydrolyzing GES-Type beta-lactamase from pseudomonas aeruginosa that contains Ile80 and Ser170 residues.
Antimicrob.Agents Chemother., 57:396-401, 2013

PubMed Abstract: A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

PubMed: 23114760
DOI: 10.1128/AAC.01784-12

実験手法

X-RAY DIFFRACTION (1.9 Å)