A hypothetical mechanism for HIV-1 integrase catalytic action: DFT modelling of a bio-mimetric environment

Fernando Bernardi, Andrea Bottoni, Marco De Vivo, Marco Garavelli, György Keserü, Gábor Náray-Szabó

Research output: Article

24 Citations (Scopus)

Abstract

Density functional theory computations for a realistic model of the HIV-1 integrase active-site/substrate complex support a single-step reaction for the hydrolysis of phosphodiester bonds, which involves a highly structured SN2-like transition state. Mediation by a stable penta-coordinated intermediate (i.e., the long time postulated dianionic phosphorane) seems lacking. These results call for an energetically favoured divalent cation requiring process coupled to a highly cooperative mechanism, which reduces the activation energy and directs the selectivity for (3′)O-P bond hydrolysis.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalChemical Physics Letters
Volume362
Issue number1-2
DOIs
Publication statusPublished - aug. 13 2002

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

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