PMID: 7544013Aug 15, 1995Paper

Human immunodeficiency virus reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by nonnucleoside inhibitors

Proceedings of the National Academy of Sciences of the United States of America
K RittingerR S Goody

Abstract

A combination of transient kinetic and equilibrium titration methods has been used to show that both primer/template and nucleotide binding to human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are two-step processes. In both cases, after initial formation of relatively weakly bound states, isomerization reactions lead to tightly bound states. In the case of deoxynucleotide binding to the reverse transcriptase-primer/template complex, the second step in the interaction is rate-limiting in the overall reaction during processive polymerization. Discrimination against incorrect nucleotides occurs both in the initial weak binding and in the second step but is purely kinetic in the second step (as opposed to thermodynamic in the first step). Nonnucleoside inhibitors have a relatively small effect on nucleotide-binding steps (overall affinity is reduced by a factor of ca. 10), while the affinity of the primer/template duplex is increased by at least a factor of 10. The major effect of nonnucleoside inhibitors is on the chemical step (nucleotide transfer).

References

Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D L RomeroL Resnick
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·S J SmerdonT A Steitz
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·D W RodgersS C Harrison
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A Jacobo-MolinaP Clark

❮ Previous
Next ❯

Citations

Jun 13, 2001·Analytical Biochemistry·I I GorshkovaR J Crouch
Feb 13, 2001·Trends in Biochemical Sciences·M V Rodnina, W Wintermeyer
Mar 12, 2011·Journal of Medicinal Chemistry·Giovanni N RovielloCarlo Pedone
Jan 24, 2012·Nature Structural & Molecular Biology·Kalyan DasEddy Arnold
Mar 3, 2010·The Journal of Biological Chemistry·Stefan ReichSven-Erik Behrens
Sep 30, 2010·The Journal of Biological Chemistry·Matthew M SchuckmannStefan G Sarafianos
Aug 5, 1999·Nucleosides & Nucleotides·R PontikisC Monneret
Dec 7, 2006·Proceedings. Biological Sciences·Victoria FurióRafael Sanjuán
Sep 2, 2009·Microbiology and Molecular Biology Reviews : MMBR·Adewunmi Onafuwa-Nuga, Alice Telesnitsky
Jun 8, 2001·Annual Review of Biochemistry·M V Rodnina, W Wintermeyer
Jun 27, 2013·Retrovirology·Eleftherios MichailidisStefan G Sarafianos
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Christian CastroCraig E Cameron
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·S H Hughes
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·D V NissleyJ N Strathern
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Matthew W Kellinger, Kenneth A Johnson
Apr 2, 2010·Cellular and Molecular Life Sciences : CMLS·Alon Herschhorn, Amnon Hizi
Feb 18, 2016·Retrovirology·Steven J SmithStephen H Hughes
Oct 25, 2014·Viruses·Pinar Iyidogan, Karen S Anderson
Apr 23, 2013·Current Opinion in Virology·Kalyan Das, Eddy Arnold
Dec 10, 2015·Journal of Molecular Graphics & Modelling·Alberto Massarotti, Antonio Coluccia
Nov 22, 2008·Journal of Molecular Biology·Stefan G SarafianosEddy Arnold
Mar 29, 2008·Virus Research·Nicolas Sluis-Cremer, Gilda Tachedjian

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.