title: The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant.
abstract: 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, 333-346]. 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.
authors.affiliation: Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bujacz
authors.forename: J
authors.initials: J
authors.lastname: Alexandratos
authors.forename: Z L
authors.initials: ZL
authors.lastname: Qing
authors.forename: C
authors.initials: C
authors.lastname: Clément-Mella
authors.forename: A
authors.initials: A
authors.lastname: Wlodawer
mesh_terms: D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012995:Solubility
chemical_list: D019427:HIV Integrase