Identification of a nucleotide binding site in HIV-1 integrase.

Drake, R R; Neamati, N; Hong, H; Pilon, A A; Sunthankar, P; Hume, S D; Milne, G W; Pommier, Y · Proc Natl Acad Sci U S A · 1998

basic_science · Level V

Where this comes from

Abstract

HIV-1 integrase is essential for viral replication and can be inhibited by antiviral nucleotides. Photoaffinity labeling with the 3'-azido-3'-deoxythymidine (AZT) analog 3',5-diazido-2', 3'-dideoxyuridine 5'-monophosphate (5N3-AZTMP) and proteolytic mapping identified the amino acid 153-167 region of integrase as the site of photocrosslinking. Docking of 5N3-AZTMP revealed the possibility for strong hydrogen bonds between the inhibitor and lysines 156, 159, and 160 of the enzyme. Mutation of these residues reduced photocrosslinking selectively. This report elucidates the binding site of a nucleotide inhibitor of HIV-1 integrase, and possibly a component of the enzyme polynucleotide binding site.

Medical subject headings