Stereo-selectivity of HIV-1 reverse transcriptase toward isomers of thymidine-5′-O-1-thiotriphosphate

Jessica Radzio, Nicolas Sluis-Cremer

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The first pre-steady-state kinetic analysis of the stereo-selective incorporation of Rp- and Sp-isomers of thymidine-5′-O-1-thiotriphosphate (TTPαS) by HIV-1 reverse transcriptase (RT) is reported. Rates of polymerization (kpol), apparent dissociation constants (K d), and substrate specificities (kpol/Kd) were measured for TTP, Rp-TTPαS, and Sp-TTPαS in the presence of Mg 2+, Mn2+, and Co2+. HIV-1 RT exhibits a strong preference to incorporate Sp-TTPαS over Rp-TTPαS in the presence of Mg2+; however, this stereo-selective preference was decreased when Mg2+ was replaced with Mn2+ and Co2+. Furthermore, HIV-1 RT exhibited no phosphorothioate elemental effects for the incorporation of Sp-TTPαS, but large elemental effects were calculated for Rp-TTPαS for each of the metals tested. These results are discussed in relation to our current understanding of the RT active-site structure and the mechanism of DNA synthesis.

Original languageEnglish (US)
Pages (from-to)1929-1933
Number of pages5
JournalProtein Science
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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