3HLW

CTX-M-9 S70G in complex with cefotaxime

3HLW の概要

• エントリーDOI: 10.2210/pdb3hlw/pdb
• 分子名称: CTX-M-9 extended-spectrum beta-lactamase, (6R,7R)-3-(acetyloxymethyl)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino-ethanoyl]amino]-8-oxo-5-thia-1-azabicy clo[4.2.0]oct-2-ene-2-carboxylic acid (3 entities in total)
• 機能のキーワード: beta-lactamase, esbl, ctx-m, ctx-m-9, beta-lactam, cephalosporin, cefotaxime, michaelis, complex, antibiotic resistance, 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: 57706.79

構造登録者

Delmas, J.,Leyssne, D.,Dubois, D.,Vazeille, E.,Robin, F.,Bonnet, R. (登録日: 2009-05-28, 公開日: 2010-06-02, 最終更新日: 2023-11-01)

主引用文献

Delmas, J.,Leyssene, D.,Dubois, D.,Birck, C.,Vazeille, E.,Robin, F.,Bonnet, R.
Structural insights into substrate recognition and product expulsion in CTX-M enzymes.
J.Mol.Biol., 400:108-120, 2010

PubMed Abstract: beta-Lactamase-mediated resistance to beta-lactam antibiotics poses a major threat to our antibiotic armamentarium. Among beta-lactamases, a significant threat comes from enzymes that hydrolyze extended-spectrum cephalosporins such as cefotaxime. Among the enzymes that exhibit this phenotype, the CTX-M family is found worldwide. These enzymes have a small active site, which makes it difficult to explain how they hydrolyze the bulky extended-spectrum cephalosporins into the binding site. We investigated noncovalent substrate recognition and product release in CTX-M enzymes using steered molecular dynamics simulation and X-ray diffraction. An arginine residue located far from the binding site favors the capture and tracking of substrates during entrance into the catalytic pocket. We show that the accommodation of extended-spectrum cephalosporins by CTX-M enzymes induced subtle changes in the active site and established a high density of electrostatic interactions. Interestingly, the product of the catalytic reaction initiates its own release because of steric hindrances and electrostatic repulsions. This suggests that there exists a general mechanism for product release for all members of the beta-lactamase family and probably for most carboxypeptidases.

PubMed: 20452359
DOI: 10.1016/j.jmb.2010.04.062

実験手法

X-RAY DIFFRACTION (1.5 Å)