中华临床感染病杂志
中華臨床感染病雜誌
중화림상감염병잡지
CHINESE JOURNAL OF CLINICAL INFECTIOUS DISEASES
2012年
2期
77-80
,共4页
β-内酰胺酶类%头孢菌素酶%进化,分子%分子对接%结合自由能
β-內酰胺酶類%頭孢菌素酶%進化,分子%分子對接%結閤自由能
β-내선알매류%두포균소매%진화,분자%분자대접%결합자유능
Beta-lactams%Cephalosporinase%Evolution,molecular%Molecular docking%Binding free energy
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.
目的 分析ADC-57型頭孢菌素酶分子進化及其對各種底物的結閤自由能.方法 用MEGA 5.0軟件中的最小進化法分析ADC-57和其他19種β-內酰胺酶的分子進化,參照同類酶CMY-2型酶作同源建模穫得ADC67型頭孢菌素酶分子的3D結構,併用ArgusLab 4.1軟件中的DOCK模塊作ADC-57型頭孢菌素酶與11種β-內酰胺類藥物底物的分子對接,最後計算酶與底物的結閤自由能值(△G).結果 ADC-57與CMY-2、DHA-1、ADC-7、ADC-56歸屬為C類β-內酰胺酶,均為頭孢菌素酶,且與ADC-56關繫最為密切.ADC-57與β-內酰胺類藥物結閤自由能下降居前3位的為阨他培南、頭孢西丁和頭孢他啶,結閤自由能下降排在後2位的為剋拉維痠和氨麯南.結論 ADC-57型頭孢菌素酶對阨他培南、頭孢西丁和頭孢他啶的催化能力高,而對剋拉維痠和氨麯南的催化能力低.分子對接分析有助于瞭解酶對各種β-內酰胺類藥物(各種底物)的水解能力.
목적 분석ADC-57형두포균소매분자진화급기대각충저물적결합자유능.방법 용MEGA 5.0연건중적최소진화법분석ADC-57화기타19충β-내선알매적분자진화,삼조동류매CMY-2형매작동원건모획득ADC67형두포균소매분자적3D결구,병용ArgusLab 4.1연건중적DOCK모괴작ADC-57형두포균소매여11충β-내선알류약물저물적분자대접,최후계산매여저물적결합자유능치(△G).결과 ADC-57여CMY-2、DHA-1、ADC-7、ADC-56귀속위C류β-내선알매,균위두포균소매,차여ADC-56관계최위밀절.ADC-57여β-내선알류약물결합자유능하강거전3위적위액타배남、두포서정화두포타정,결합자유능하강배재후2위적위극랍유산화안곡남.결론 ADC-57형두포균소매대액타배남、두포서정화두포타정적최화능력고,이대극랍유산화안곡남적최화능력저.분자대접분석유조우료해매대각충β-내선알류약물(각충저물)적수해능력.
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.
