Crystal structures of catalytic core domain of BIV integrase: implications for the interaction between integrase and target DNA  

作　　者：Xue Yao Shasha Fang Wentao Qiao Yunqi Geng Yuequan Shen 

机构地区：[1]Tianjin Key Laboratory of Protein Science,College of Life Sciences,Nankai University,94 Weijin Road,Tianjin 300071,China [2]Key Laboratory of Molecular Microbiology and Biotechnology(Ministry of Education),the College of Life Science,Nankai University,94 Weijin Road,Tianjin 300071,China

出　　处：《Protein & Cell》2010年第4期363-370,共8页蛋白质与细胞（英文版）

基　　金：This study was supported by grants from the Ministry of Science and Technology of China(Grant Nos.2007CB914301,2009CB825504,2006AA02A319,2006AA020502);the Ministry of Health of China(Grant No.2008ZX10001-002);the National Natural Science Foundation of China(Grant Nos.30770428,30940015);the TBR programs(Grant Nos.08QTPTJC28200,08SYSYTC00200,07JCYBJC19200).

摘　　要：Integrase plays a critical role in the recombination of viral DNA into the host genome.Therefore,over the past decade,it has been a hot target of drug design in the fight against type 1 human immunodeficiency virus(HIV-1).Bovine immunodeficiency virus(BIV)integrase has the same function as HIV-1 integrase.We have determined crystal structures of the BIV integrase catalytic core domain(CCD)in two different crystal forms at a resolution of 2.45Åand 2.2Å,respectively.In crystal form I,BIV integrase CCD forms a back-to-back dimer,in which the two active sites are on opposite sides.This has also been seen in many of the CCD structures of HIV-1 integrase that were determined previously.However,in crystal form II,BIV integrase CCD forms a novel face-toface dimer in which the two active sites are close to each other.Strikingly,the distance separating the two active sites is approximately 20Å,a distance that perfectly matches a 5-base pair interval.Based on these data,we propose a model for the interaction of integrase with its target DNA,which is also supported by many published biochemical data.Our results provide important clues for designing new inhibitors against HIV-1.

关 键 词：bovine immunodeficiency virus INTEGRASE catalytic core domain crystal structure DIMERIZATION 

分 类 号：S85[农业科学—兽医学]