Crystal structures of catalytic core domain of BIV integrase: implications for the interaction between integrase and target DNA.
10.1007/s13238-010-0047-5
- Author:
Xue YAO
1
;
Shasha FANG
1
;
Wentao QIAO
2
;
Yunqi GENG
3
;
Yuequan SHEN
4
Author Information
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.
3. 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.
4. Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China. yshen@nankai.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Catalytic Domain;
genetics;
Cattle;
DNA;
genetics;
DNA, Viral;
HIV-1;
genetics;
metabolism;
Humans;
Immunodeficiency Virus, Bovine;
enzymology;
genetics;
Integrases;
chemistry;
genetics;
metabolism
- From:
Protein & Cell
2010;1(4):363-370
- CountryChina
- Language:English
-
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.
