Crystal Structure of the Catalytic Domain of HIV-1 Integrase: Similarity to Other Polynucleotidyl Transferases

TLDR

HIV integrase inserts viral DNA into the host genome and is essential for replication, and its catalytic core domain shares a polynucleotidyl transferase fold with enzymes such as ribonuclease H and RuvC. The 2.5‑Å crystal structure of residues 50–212 reveals a five‑stranded β‑sheet core flanked by helices, positions two conserved catalytic carboxylates analogous to ribonuclease H, and shows the domain dimerizes via a 1300‑Ų solvent‑inaccessible interface.

Abstract

HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 Å resolution. The central feature of the structure is a five-stranded β sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with an extensive solvent-inaccessible interface of 1300 Å 2 per monomer.