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