Molecular modeling of human APOBEC3G to predict the binding modes of the inhibitor compounds IMB26 and IMB35  

作　　者：Zhixin Zhang Congjie Zhai Zeyun Mi Jiwei Ding Yongxin Zhang Xing Shi Xiaoyu Li Liyan Yu Zhuorong Li Jiandong Jiang Jinming Zhou Shan Cen 

机构地区：[1]Institute of Medicinal Biotechnology,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China [2]Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China

出　　处：《Acta Pharmaceutica Sinica B》2013年第4期239-244,共6页药学学报（英文版）

基　　金：part by 973 program(2012C B911102);the National S&T Major Special Project on Major New Drug Innovation(2012ZX09102101-018);the National S&T International Collaboration 2010DFA31580(J.D.J.)and 2010DFB30870(Q.J.).

摘　　要：APOBEC3G(A3G)is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication.The virally encoded protein Vif binds to A3G and induces its degradation,thereby counteracting the antiviral activity of A3G.Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development.Currently,there is an urgent need for understanding the three dimensional structure of full-length A3G.In this work,we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2(APO2)and the catalytic domain structure of A3G.Two compounds,IMB26 and IMB35,which have been shown to bind to A3G and block degradation by Vif,were docked into the A3G model and the binding modes were generated for further analysis.The results may be used to design or optimize molecules targeting Vif–A3G interaction,and lead to the development of novel anti-HIV drugs.

关 键 词：Host restriction factor APOBEC3G HIV Molecular modeling Anti-HIV drug 

分 类 号：O64[理学—物理化学]