6G9T

CRYSTAL STRUCTURE OF CMY-136 class C BETA-LACTAMASE

6G9T の概要

• エントリーDOI: 10.2210/pdb6g9t/pdb
• 分子名称: Beta-lactamase, PHOSPHATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: class c beta-lactamase cmy-136-histag, antibiotic, dimer, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83557.43

構造登録者

Zavala, A.,Retailleau, P.,Naas, T.,Iorga, B. (登録日: 2018-04-11, 公開日: 2019-02-27, 最終更新日: 2024-01-17)

主引用文献

Zavala, A.,Retailleau, P.,Elisee, E.,Iorga, B.I.,Naas, T.
Genetic, Biochemical, and Structural Characterization of CMY-136 beta-Lactamase, a Peculiar CMY-2 Variant.
Acs Infect Dis., 5:528-538, 2019

PubMed Abstract: With the widespread use and abuse of antibiotics for the past decades, antimicrobial resistance poses a serious threat to public health nowadays. β-Lactams are the most used antibiotics, and β-lactamases are the most widespread resistance mechanism. Class C β-lactamases, also known as cephalosporinases, usually do not hydrolyze the latest and most potent β-lactams, expanded spectrum cephalosporins and carbapenems. However, the recent emergence of extended-spectrum AmpC cephalosporinases, their resistance to inhibition by classic β-lactamase inhibitors, and the fact that they can contribute to carbapenem resistance when paired with impermeability mechanisms, means that these enzymes may still prove worrisome in the future. Here we report and characterize the CMY-136 β-lactamase, a Y221H point mutant derivative of CMY-2. CMY-136 confers an increased level of resistance to ticarcillin, cefuroxime, cefotaxime, and ceftolozane/tazobactam. It is also capable of hydrolyzing ticarcillin and cloxacillin, which act as inhibitors of CMY-2. X-ray crystallography and modeling experiments suggest that the hydrolytic profile alterations seem to be the result of an increased flexibility and altered conformation of the Ω-loop, caused by the Y221H mutation.

PubMed: 30788955
DOI: 10.1021/acsinfecdis.8b00240

実験手法

X-RAY DIFFRACTION (1.6 Å)