Allosteric regulation of HIV-1 reverse transcriptase by ATP for nucleotide selection.

PloS One
Masaru YokoyamaHironori Sato

Abstract

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a DNA polymerase that converts viral RNA genomes into proviral DNAs. How HIV-1 RT regulates nucleotide selectivity is a central issue for genetics and the nucleoside analog RT inhibitor (NRTI) resistance of HIV-1. Here we show that an ATP molecule at physiological concentrations acts as an allosteric regulator of HIV-1 RT to decrease the K(m) value of the substrate, decrease the k(cat) value, and increase the K(i) value of NRTIs for RT. Computer-assisted structural analyses and mutagenesis studies suggested the positions of the ATP molecule and NRTI-resistance mutations during a catalytic reaction, which immediately predict possible influences on nucleotide insertion into the catalytic site, the DNA polymerization, and the excision reaction. These data imply that the ATP molecule and NRTI mutations can modulate nucleotide selectivity by altering the fidelity of the geometric selection of nucleotides and the probability of an excision reaction.

References

Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P A FurmanH Mitsuya
Nov 25, 1988·Science·B D PrestonL A Loeb
Nov 25, 1988·Science·J D RobertsT A Kunkel
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J PetruskaI Tinoco
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·K RittingerR S Goody
Nov 9, 1994·Molecular and Cellular Biochemistry·T W Traut
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·M F Goodman
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·P R MeyerW A Scott
Aug 31, 2000·Annual Review of Biochemistry·T A Kunkel, K Bebenek
Oct 6, 2001·Science·D Baker, A Sali
Mar 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sean J JohnsonLorena S Beese
Feb 28, 2004·The Journal of Biological Chemistry·Thomas A Kunkel
Mar 16, 2004·Cell·Dmitry TemiakovDmitry G Vassylyev
Jan 16, 2007·Journal of Molecular Biology·Aaron A ThompsonOlve B Peersen
Feb 19, 2008·Journal of Chemical Information and Modeling·Junichi GotoNoriaki Hirayama
Oct 7, 2008·Nature Structural & Molecular Biology·Kotaro ShirakawaTakashi Uchiyama
Nov 22, 2008·Journal of Molecular Biology·Stefan G SarafianosEddy Arnold

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Methods Mentioned

BETA
PCR
size exclusion chromatography
electrophoresis

Software Mentioned

Molecular Operating Environment MOE
Igor Pro
MOE
ASEDock2005
Molecular

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