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