Structural probing of the HIV-1 polypurine tract RNA:DNA hybrid using classic nucleic acid ligands.

Nucleic Acids Research
Kevin B TurnerDaniele Fabris

Abstract

The interactions of archetypical nucleic acid ligands with the HIV-1 polypurine tract (PPT) RNA:DNA hybrid, as well as analogous DNA:DNA, RNA:RNA and swapped hybrid substrates, were used to probe structural features of the PPT that contribute to its specific recognition and processing by reverse transcriptase (RT). Results from intercalative and groove-binding ligands indicate that the wild-type PPT hybrid does not contain any strikingly unique groove geometries and/or stacking arrangements that might contribute to the specificity of its interaction with RT. In contrast, neomycin bound preferentially and selectively to the PPT near the 5'(rA)(4):(dT)(4) tract and the 3' PPT-U3 junction. Nuclear magnetic resonance data from a complex between HIV-1 RT and the PPT indicate RT contacts within the same regions highlighted on the PPT by neomycin. These observations, together with the fact that the sites are correctly spaced to allow interaction with residues in the ribonuclease H (RNase H) active site and thumb subdomain of the p66 RT subunit, suggest that despite the long cleft employed by RT to make contact with nucleic acids substrates, these sites provide discrete binding units working in concert to determine not only specific PP...Continue Reading

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Citations

Nov 10, 2009·Journal of the American Society for Mass Spectrometry·Daniele Fabris
Jun 10, 2011·Analytical Chemistry·D Fabris
Jan 24, 2012·Analytical Chemistry·Feng XianAlan G Marshall
Mar 23, 2013·Journal of the American Chemical Society·William StephensonPan T X Li
Feb 15, 2012·International Journal of Mass Spectrometry·D FabrisJ A Wilhide
Aug 12, 2009·Biochimica Et Biophysica Acta·Matthias GötteStuart F J Le Grice
Feb 7, 2015·PloS One·Verónica Quintero-HernándezErnesto Ortiz
Sep 10, 2014·Physical Chemistry Chemical Physics : PCCP·Josephine Abi-Ghanem, Valérie Gabelica
Oct 1, 2021·Chemical Reviews·Eric LargyValérie Gabelica
Dec 24, 2021·Mass Spectrometry Reviews·Thomas Kenderdine, Dan Fabris

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Methods Mentioned

BETA
nuclear magnetic resonance
electrophoresis
NMR
footprinting
chemical
fluorescence spectroscopy
two hybrids

Software Mentioned

TopSpin
XMASS
Origin

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