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

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.