Molecular evolution and binding free energy analysis of substrates of cephalosporinase ADC-57

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ZHOU Jun(Department of Respiratory Medicine, the First People' s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China)
WANG Yu-yue()
ZHANG Qiu-di(Department of Respiratory Medicine, the First People' s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China)
Journal Title:
Chinese Journal of Clinical Infectious Diseases
Volume 05, Issue 02, 2012
Key Word:
Beta-lactams;Cephalosporinase;Evolution, molecular;Molecular docking;Binding free energy

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.

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