Enthalpy-entropy compensation and cooperativity as thermodynamic epiphenomena of structural flexibility in ligand-receptor interactions.

Journal of Molecular Biology
Andrea Ferrante, Jack Gorski

Abstract

Ligand binding is a thermodynamically cooperative process in many biochemical systems characterized by the conformational flexibility of the reactants. However, the contribution of conformational entropy to cooperativity of ligation needs to be elucidated. Here, we perform kinetic and thermodynamic analyses on a panel of cycle-mutated peptides, derived from influenza H3 HA(306-319), interacting with wild type and a mutant HLA-DR. We observe that, within a certain range of peptide affinity, this system shows isothermal entropy-enthalpy compensation (iEEC). The incremental increases in conformational entropy measured as disruptive mutations are added in the ligand or receptor are more than sufficient in magnitude to account for the experimentally observed lack of free-energy decrease cooperativity. Beyond this affinity range, compensation is not observed, and therefore, the ability of the residual interactions to form a stable complex decreases in an exponential fashion. Taken together, our results indicate that cooperativity and iEEC constitute the thermodynamic epiphenomena of the structural fluctuation that accompanies ligand-receptor complex formation in flexible systems. Therefore, ligand binding affinity prediction needs to...Continue Reading

References

Feb 1, 1992·Immunology Today·S Sadegh-Nasseri, R N Germain
Apr 5, 1992·Journal of Molecular Biology·A Horovitz, A R Fersht
Sep 12, 1991·Nature·S Sadegh-Nasseri, R N Germain
Aug 5, 1990·Journal of Molecular Biology·A Horovitz, A R Fersht
Oct 20, 1989·Journal of Molecular Biology·J H HaM T Record
Apr 9, 2002·Journal of Biosciences·Athel Cornish-Bowden
Mar 27, 2003·Journal of the American Chemical Society·Sutjano JusufPaul H Axelsen
Sep 23, 2003·Biophysical Chemistry·Rufus Lumry
Dec 4, 2003·Chemistry & Biology·Christopher A Hunter, Salvador Tomas
Apr 13, 2005·Biochemistry·Matthew W Anderson, Jack Gorski
Feb 1, 1958·Proceedings of the National Academy of Sciences of the United States of America·D E Koshland
Jan 24, 2007·Physical Chemistry Chemical Physics : PCCP·Zheng Li, Themis Lazaridis
Sep 12, 2009·Angewandte Chemie·Christopher A Hunter, Harry L Anderson
Aug 21, 2013·PloS One·Yuri O PoluektovScheherazade Sadegh-Nasseri

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Citations

May 10, 2013·Annual Review of Biophysics·John D Chodera, David L Mobley
Jan 3, 2016·Drug Discovery Today. Technologies·Franz-Josef Meyer-Almes
Sep 9, 2016·The Journal of Physical Chemistry. B·Animesh PanSatya P Moulik
Jan 25, 2017·Physical Chemistry Chemical Physics : PCCP·Srinivasa M GopalLars V Schäfer
Dec 3, 2016·Bioorganic & Medicinal Chemistry·Vladimir SofiyevMiriam Gochin
Oct 24, 2017·Soft Matter·Fernando Vargas-LaraJack F Douglas
Aug 27, 2013·Monatshefte für chemie·Liviu Movileanu, Eric A Schiff
Sep 7, 2019·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Doreen Niether, Simone Wiegand
Jun 28, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea FerranteMargaret J Castellini
May 28, 2015·Chemistry : a European Journal·Teng ZhangLixin Wu
Mar 5, 2020·Journal of Bioenergetics and Biomembranes·César Muñoz-BacasehuaElisa M Valenzuela-Soto
Sep 4, 2020·Journal of Molecular Recognition : JMR·César Muñoz-BacasehuaElisa M Valenzuela-Soto
Dec 6, 2014·ACS Chemical Biology·Belete R ChenekeLiviu Movileanu

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