Molecular mechanisms of antibiotic resistance:: QM/MM modelling of deacylation in a class A β-lactamase

被引：55

作者：

Hermann, JC ^{[1
]}

Ridder, L

Hötje, HD

Mulholland, AJ

机构：

[1] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England

[2] Univ Calif San Francisco, Dept Pharmceut Chem, San Francisco, CA 94143 USA

[3] NV Organon, Mol Design & Informat, NL-5340 BH Oss, Netherlands

[4] Univ Dusseldorf, Inst Pharmazeut Chem, D-40225 Dusseldorf, Germany

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2006年 / 4卷 / 02期

关键词：

D O I：

10.1039/b512969a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Modelling of the first step of the deacylation reaction of benzylpenicllin in the E. coli TEM1 P-lactamase (with B3LYP/6-31G + (d)//AM1-CHARMM22 quantum mechanics/molecular mechanics methods) shows that a mechanism in which Glu166 acts as the base to deprotonate a conserved water molecule is both energetically and structurally consistent with experimental data; the results may assist the design of new antibiotics and P-lactamase inhibitors.

引用

页码：206 / 210

页数：5

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