Peptides that bind the HIV-1 integrase and modulate its enzymatic activity -kinetic studies and mode of action

Aviad Levin, Hadar Benyamini, Zvi Hayouka, Assaf Friedler, Abraham Loyter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Several peptides that specifically bind the HIV-1 integrase (IN) and either inhibit or stimulate its enzymatic activity were developed in our laboratories. Kinetic studies using 3′-end processing and strand-transfer assays were performed to study the mode of action of these peptides. The effects of the various peptides on the interaction between IN and its substrate DNA were also studied by fluorescence anisotropy. On the basis of our results, we divided these IN-interacting peptides into three groups: (a) IN-inhibitory peptides, whose binding to IN decrease its affinity for the substrate DNA -these peptides increased the Km of the IN-DNA interaction, and were thus inhibitory; (b) peptides that slightly increased the Km of the IN-DNA interaction, but in addition modified the Vmax and Kcat values of the IN, and thus stimulated or inhibited IN activity, respectively; and (c) peptides that bound IN but had no effect on its enzymatic activity. We elucidated the approximate binding sites of the peptides in the structure of IN, providing structural insights into their mechanism of action. The IN-stimulating peptide bound IN in several specific sites that did not bind any of the inhibitory peptides. This may account for its unique activity.

Original languageAmerican English
Pages (from-to)316-330
Number of pages15
JournalFEBS Journal
Volume278
Issue number2
DOIs
StatePublished - Jan 2011

Keywords

  • HIV-1
  • integrase
  • peptides

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