摘要目的 分析ADC-57型头孢菌素酶分子进化及其对各种底物的结合自由能.方法 用MEGA 5.0软件中的最小进化法分析ADC-57和其他19种β-内酰胺酶的分子进化,参照同类酶CMY-2型酶作同源建模获得ADC67型头孢菌素酶分子的3D结构,并用ArgusLab 4.1软件中的DOCK模块作ADC-57型头孢菌素酶与11种β-内酰胺类药物底物的分子对接,最后计算酶与底物的结合自由能值(△G).结果 ADC-57与CMY-2、DHA-1、ADC-7、ADC-56归属为C类β-内酰胺酶,均为头孢菌素酶,且与ADC-56关系最为密切.ADC-57与β-内酰胺类药物结合自由能下降居前3位的为厄他培南、头孢西丁和头孢他啶,结合自由能下降排在后2位的为克拉维酸和氨曲南.结论 ADC-57型头孢菌素酶对厄他培南、头孢西丁和头孢他啶的催化能力高,而对克拉维酸和氨曲南的催化能力低.分子对接分析有助于了解酶对各种β-内酰胺类药物(各种底物)的水解能力.

abstractsObjective 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.