HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: ps.051445605v1 14/7/1929    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Radzio, J. Articles by Sluis-Cremer, N. Search for Related Content PubMed PubMed Citation Articles by Radzio, J. Articles by Sluis-Cremer, N. Social Bookmarking                   What's this?

FOR THE RECORD

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

University of Pittsburgh School of Medicine, Division of Infectious Diseases, Pittsburgh, Pennsylvania 15261, USA

(RECEIVED March 8, 2005; FINAL REVISION April 13, 2005; ACCEPTED April 17, 2005)

The first pre-steady-state kinetic analysis of the stereo-selective incorporation of Rp- and Sp-isomers of thymidine-5'-O-1-thiotriphosphate (TTPS) by HIV-1 reverse transcriptase (RT) is reported. Rates of polymerization (k_pol), apparent dissociation constants (K_d), and substrate specificities (k_pol/K_d) were measured for TTP, Rp-TTPS, and Sp-TTPS in the presence of Mg²⁺, Mn²⁺, and Co²⁺. HIV-1 RT exhibits a strong preference to incorporate Sp-TTPS over Rp-TTPS 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-TTPS, but large elemental effects were calculated for Rp-TTPS 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.

Keywords: HIV-1; reverse transcriptase; DNA polymerization; stereo-selectivity; pre-steady-state; elemental effect

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.051445605.

Reprint requests to: Nicolas Sluis-Cremer, University of Pittsburgh School of Medicine, Division of Infectious Diseases, S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA; e-mail: CremerN{at}dom.pitt.edu; fax: (412) 648-8521.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Q. Xia, J. Radzio, K. S. Anderson, and N. Sluis-Cremer Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses Protein Sci., August 1, 2007; 16(8): 1728 - 1737. [Abstract] [Full Text] [PDF]