title: Crystal structures of catalytic core domain of BIV integrase: implications for the interaction between integrase and target DNA.
abstract: 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 2.45 Å and 2.2 Å, 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-to-face dimer in which the two active sites are close to each other. Strikingly, the distance separating the two active sites is approximately 20 Å, 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.
authors.affiliation: Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.|Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education), the College of Life Science, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yao
authors.affiliation: Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Fang
authors.affiliation: Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education), the College of Life Science, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education), the College of Life Science, Nankai University, 94 Weijin Road, Tianjin, 300071, China. gengyq@nankai.edu.cn.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China. yshen@nankai.edu.cn.
authors.forename: Yuequan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D002417:Cattle; D004247:DNA / Q000235:genetics; D004279:DNA, Viral; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016087:Immunodeficiency Virus, Bovine / Q000201:enzymology* / Q000235:genetics; D019426:Integrases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D004247:DNA; D019426:Integrases