Crystal structures of catalytic core domain of BIV integrase: implications for the interaction between integrase and target DNA
Protein & Cell
;
(12): 363-370, 2010.
Article
in English
| WPRIM
| ID: wpr-757754
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
DNA
/
DNA, Viral
/
Chemistry
/
HIV-1
/
Immunodeficiency Virus, Bovine
/
Integrases
/
Catalytic Domain
/
Genetics
/
Metabolism
Limits:
Animals
/
Humans
Language:
English
Journal:
Protein & Cell
Year:
2010
Type:
Article
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