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Ile178 of HIV-1 reverse transcriptase is critical for inhibiting the viral integrase

Iris Oz Gleenberg1, Yehuda Goldgur, Amnon Hizi

  • 1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Biochemical and Biophysical Research Communications
|October 12, 2007
PubMed

HIV-1 reverse transcriptase (RT) was shown to inhibit in vitro the viral integrase (IN). We have reported previously that an RT-derived 20-residue peptide binds IN and inhibits its enzymatic activities. In this peptide, Leu168, Phe171, Gln174, and Ile178 were predicted to be involved in IN inhibition. In the presented study, these residues were mutagenized and the resulting peptides were tested for binding and inhibiting IN activities. Ile178 was found to be the major contributor to IN inhibition, probably by interacting with IN residue Gly149. As Gly149 is a key IN residue, this inhibition probably results from a steric hindrance of the IN active site.

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