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Licensed Unlicensed Requires Authentication Published by De Gruyter July 8, 2014

Thermodynamic signatures in macromolecular interactions involving conformational flexibility

  • Anja Menzel , Piotr Neumann , Christian Schwieger and Milton T. Stubbs EMAIL logo
From the journal Biological Chemistry

Abstract

The energetics of macromolecular interactions are complex, particularly where protein flexibility is involved. Exploiting serendipitous differences in the plasticity of a series of closely related trypsin variants, we analyzed the enthalpic and entropic contributions accompanying interaction with L45K-eglin C. Binding of the four variants show significant differences in released heat, although the affinities vary little, in accordance with the principle of enthalpy-entropy compensation. Binding of the most disordered variant is almost entirely enthalpically driven, with practically no entropy change. As structures of the complexes reveal negligible differences in protein-inhibitor contacts, we conclude that solvent effects contribute significantly to binding affinities.


Dedicated to Professor Dr. Gerhard Klebe on the occasion of his 60th birthday.



Corresponding author: Milton T. Stubbs, Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 3, D-06120 Halle/Saale, Germany, e-mail:
aPresent address: Institut für Rechtsmedizin, Otto-von-Guerike-Universität, Leipziger Straße 44, D-39120 Magdeburg, GermanybPresent address: Institut für Mikrobiologie und Genetik, Georg-August-Universität, Justus-von-Liebig-Weg 11, D-37077 GÖttingen, Germany

Acknowledgments

This work was supported by the DFG Graduiertenkolleg 1026 ‘Conformational transitions in macromolecular interactions’.

  1. 1

    The disorder is reflected in higher temperature factors of the final model in this region; a more detailed analysis of these has not been carried out because the link between crystallographic B factors and dynamics is questionable, demonstrated recently for a set of representative proteins (Reichert et al., 2012)

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Supplemental Material: The online version of this article (DOI 10.1515/hsz-2014-0177) offers supplementary material, available to authorized users.


Received: 2014-3-27
Accepted: 2014-5-5
Published Online: 2014-7-8
Published in Print: 2014-7-1

©2014 by Walter de Gruyter Berlin/Boston

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