The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant

FEBS Letters

Alexandratos, Jerry²  Clément-Mella, Christine¹  Zhou-Liu, Qing¹  Wlodawer, Alexander²  Bujacz, Grzegorz² 

[1] Service de Biochimie, Rhône-Poulenc Rorer SA, 94403 Vitry sur Seine, France;Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, MD 21702, USA

关键词: Integrase;    Active site;    Disorder;    Metal binding;    AIDS;    acquired immunodeficiency syndrome;    ASV;    avian sarcoma virus;    HIV-1;    human immunodeficiency virus type 1;    IN;    integrase;    PEG;    polyethylene glycol;   

DOI  :  10.1016/S0014-5793(96)01236-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We solved the structure and traced the complete active site of the catalytic domain of the human immunodeficiency virus type 1 integrase (HIV-1 IN) with the F185H mutation. The only previously available crystal structure, the F185K mutant of this domain, lacks one of the catalytically important residues, E152, located in a stretch of 12 disordered residues [Dyda et al. (1994) Science 266, 1981–1986]. It is clear, however, that the active site of HIV-1 IN observed in either structure cannot correspond to that of the functional enzyme, since the cluster of three conserved carboxylic acids does not create a proper metal-binding site. The conformation of the loop was compared with two different conformations found in the catalytic domain of the related avian sarcoma virus integrase [Bujacz et al. (1995) J. Mol. Biol. 253, 333-246]. Flexibility of the active site region of integrases may be required in order for the enzyme to assume a functional conformation in the presence of substrate and/or cofactors.

【 授权许可】

Unknown