Identification of amino acids in HIV-2 integrase involved in site-specific hydrolysis and alcoholysis of viral DNA termini

Dik C. Van Gent, Antoinette A.M. Oude Groeneger, Ronald H.A. Plasterk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

55 Citations (Scopus)

Abstract

The human immunodeficiency virus integrase (HIV IN) protein cleaves two nucleotides off the 3′ end of viral DNA and subsequently integrates the viral DNA into target DNA. IN exposes a specific phosphodiester bond near the viral DNA end to nucleophilic attack by water or other nucleophiles, such as glycerol or the 3′ hydroxyl group of the viral DNA molecule itself. Wild-type IN has a preference for water as the nucleophile; we here describe a class of IN mutants that preferentially use the 3′ hydroxyl group of viral DNA as nucleophile. The amino acids that are altered in this class of mutants map near the putative active-site residues Asp-116 and Glu-152. These results support a model in which multiple amino acid side-chains are involved in presentation of the (soluble) nucleophile. IN is probably active as an oligomeric complex, in which the subunits have non-equivalent roles; we here report that nucleophile selection is determined by the subunit that supplies the active site.

Original languageEnglish
Pages (from-to)3373-3377
Number of pages5
JournalNucleic Acids Research
Volume21
Issue number15
DOIs
Publication statusPublished - 25 Jul 1993

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