CRYSTAL-STRUCTURES OF THE CATALYTIC DOMAIN OF HIV-1 INTEGRASE FREE AND COMPLEXED WITH ITS METAL COFACTOR - HIGH-LEVEL OF SIMILARITY OF THE ACTIVE-SITE WITH OTHER VIRAL INTEGRASES

Human immunodeficiency virus (HIV) integrase is the enzyme responsible for insertion of a DNA copy of the viral genome into host DNA, an ess ential step in the replication cycle of HIV. HIV-1 integrase comprises three functional and structural domains: an N-terminal zinc-binding d omain, a catalytic core domain and a C-terminal DNA-binding domain. Th e catalytic core domain with the F185H mutation has been crystallized without sodium cacodylate in a new crystal form, free and complexed wi th the catalytic metal Mg2+. The structures have been determined and r efined to about 2.2 Angstrom. Unlike the previously reported structure s, the three active-site carboxylate residues (D,D-35-E motif) are wel l. ordered and both aspartate residues delineate a proper metal-bindin g site. Comparison of the active binding site of this domain with that of other members from the polynucleotidyl transferases superfamily sh ows a high level of similarity, providing a confident template for the design of antiviral agents. (C) 1998 Academic Press.