Entropic Enhancement of Protein-DNA Affinity by Oxygen-to-Sulfur Substitution in DNA Phosphate

Biophysical Journal
Levani ZandarashviliJunji Iwahara

Abstract

Dithioation of DNA phosphate is known to enhance binding affinities, at least for some proteins. We mechanistically characterized this phenomenon for the Antennapedia homeodomain-DNA complex by integrated use of fluorescence, isothermal titration calorimetry, NMR spectroscopy, and x-ray crystallography. By fluorescence and isothermal titration calorimetry, we found that this affinity enhancement is entropy driven. By NMR, we investigated the ionic hydrogen bonds and internal motions of lysine side-chain NH3(+) groups involved in ion pairs with DNA. By x-ray crystallography, we compared the structures of the complexes with and without dithioation of the phosphate. Our NMR and x-ray data show that the lysine side chain in contact with the DNA phosphate becomes more dynamic upon dithioation. Our thermodynamic, structural, and dynamic investigations collectively suggest that the affinity enhancement by the oxygen-to-sulfur substitution in DNA phosphate is largely due to an entropic gain arising from mobilization of the intermolecular ion pair at the protein-DNA interface.

References

Nov 4, 1976·Journal of Molecular Biology·M T RecordP De Haseth
Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·W S MarshallM H Caruthers
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M AffolterW J Gehring
Mar 12, 1993·Science·W S Marshall, M H Caruthers
May 20, 1994·Journal of Molecular Biology·J E LadburyP B Sigler
Jul 2, 1996·Biochemistry·L CumminsM H Caruthers
Jan 1, 1997·Molecular Medicine Today·R W Wagner, W M Flanagan
Feb 21, 1998·Trends in Biotechnology·G M Clore, A M Gronenborn
Aug 12, 1998·Nature Structural Biology·S A DamesA T Alexandrescu
Dec 28, 1999·Bioorganic & Medicinal Chemistry Letters·X YangD G Gorenstein
Oct 31, 2000·Journal of Molecular Biology·T A WilkinsonY Chen
Jan 4, 2006·Biochemistry·Anatoly I DraganPeter L Privalov
Mar 23, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jay Painter, Ethan A Merritt
Oct 16, 2007·Nature Chemical Biology·Lianrong WangPeter C Dedon
Jul 10, 2008·Physical Chemistry Chemical Physics : PCCP·Daryl L Howard, Henrik G Kjaergaard
Jul 23, 2009·Journal of the American Chemical Society·Marimuthu Krishnan, Jeremy C Smith
Jul 25, 2009·Nucleic Acids Research·R LaveryK Zakrzewska
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Dec 29, 2010·Journal of the American Chemical Society·Alexandre EsadzeJunji Iwahara
Feb 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lianrong WangPeter C Dedon
May 20, 2011·Journal of the American Chemical Society·Levani ZandarashviliJunji Iwahara
Oct 25, 2011·Expert Opinion on Therapeutic Patents·Roberto Gambari
Jan 21, 2012·Nature Reviews. Drug Discovery·Ryszard KoleSidney Altman
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Jeffrey J HeaddPaul D Adams
Sep 11, 2013·Advances in Protein Chemistry and Structural Biology·Levani ZandarashviliJunji Iwahara
Jan 13, 2015·Methods : a Companion to Methods in Enzymology·Lee FreiburgerAnthony Mittermaier

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Citations

Oct 6, 2015·Biomolecules·Junji IwaharaLevani Zandarashvili
Feb 18, 2016·The Journal of Physical Chemistry Letters·Levani ZandarashviliJunji Iwahara
Jun 12, 2016·Nucleic Acids Research·Alexandre EsadzeJunji Iwahara
Jul 8, 2016·Transcription·Catherine A KemmeJunji Iwahara
Aug 28, 2016·Nucleic Acids Research·N Dinuka AbeydeeraXianbin Yang
Sep 30, 2016·The Journal of Physical Chemistry. B·Abhijnan ChattopadhyayJunji Iwahara
Aug 3, 2017·International Journal of Molecular Sciences·Shuaijian NiGe Zhang
Aug 16, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dan NguyenJunji Iwahara
Feb 28, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Thais KroetzFabiano S Rodembusch
Sep 2, 2016·Current Protocols in Nucleic Acid Chemistry·Xianbin Yang
Nov 20, 2019·Angewandte Chemie·Channing C PletkaJunji Iwahara
Jun 9, 2016·Chembiochem : a European Journal of Chemical Biology·Dan NguyenJunji Iwahara
Jul 20, 2020·Journal of Biomolecular NMR·Ridvan NepravishtaJunji Iwahara
Dec 3, 2016·Current Protocols in Nucleic Acid Chemistry·Xinhui LouXianbin Yang
Dec 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Binhan YuJunji Iwahara
Mar 24, 2020·Journal of the American Chemical Society·Malwina Hyjek-SkładanowskaMarcin Nowotny
Jun 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Binhan YuJunji Iwahara
Aug 28, 2020·Accounts of Chemical Research·Binhan YuJunji Iwahara
Nov 17, 2021·The Journal of Physical Chemistry Letters·Xi WangJunji Iwahara

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