CRYSTAL-STRUCTURE OF THE CATALYTIC DOMAIN OF HIV-1 INTEGRASE - SIMILARITY TO OTHER POLYNUCLEOTIDYL TRANSFERASES

HIV integrase is the enzyme responsible for inserting the viral DNA in to the host chromosome; it is essential for HIV replication. The cryst al structure of the catalytically active core domain (residues 50 to 2 12) of HIV-7 integrase was determined at 2.5 Angstrom resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases tha t includes ribonuclease H and the Holliday junction resolvase RuvC. Th e active site region is identified by the position of two of the conse rved carboxylate residues essential for catalysis, which are located a t similar positions in ribonuclease H. In the crystal, two molecules f orm a dimer with an extensive solvent-inaccessible interface of 1300 A ngstrom(2) per monomer.