Molecular evolution and binding free energy analysis of substrates of cephalosporinase ADC-57
10.3760/cma.j.issn.1674-2397.2012.02.004
- VernacularTitle:ADC-57型头孢菌素酶分子进化及与底物结合自由能分析
- Author:
Jun ZHOU
;
Yuyue WANG
;
Qiudi ZHANG
- Publication Type:Journal Article
- Keywords:
Beta-lactams;
Cephalosporinase;
Evolution,molecular;
Molecular docking;
Binding free energy
- From:
Chinese Journal of Clinical Infectious Diseases
2012;05(2):77-80
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze molecular evolution and binding free energies of cephalosporinase ADC-57.Methods Minimum Evolution method in MEGA 5.0 was used to analyze molecular evolution of cephalosporinase ADC-57 and other 19 kinds of beta-lactamases.Tertiary structure of ADC-57 was predicted by homology modeling referring to tertiary structure of CMY-2.The molecular docking of ADC-57 to 11kinds of beta-lactams substrates was performed using DOCK module in ArgusLab 4.1and the binding free energies (△G) was calculated.Results ADC-57,CMY-2,DHA-1,ADC-7,ADC-56 were all belong to class C beta-lactamase,and molecular evolution between ADC-57 and ADC-56 was closest.The top three antibiotics with declining binding free energy of beta-lactams were ertapenem,cefoxitin and ceftazidine,while the last two were clavulanic acid and aztreonam.Conclusions Catalytic activities of cephalosporinase ADC-57 to ertapenem,cefoxitin and ceftazidine are high,while to clavulanic acid and aztreonam are low. Hydrolytic activities of enzyme to beta-lactams (substrates) can be analyzed by molecular docking.
