Enthalpy/entropy compensation effects from cavity desolvation underpin broad ligand binding selectivity for rat odorant binding protein 3

Portman, Katherine L., Long, Jed, Carr, Stephen, Briand, Loic, Winzor, Donald J., Searle, Mark S. and Scott, David J. (2014) Enthalpy/entropy compensation effects from cavity desolvation underpin broad ligand binding selectivity for rat odorant binding protein 3. Biochemistry, 53 14: 2371-2379. doi:10.1021/bi5002344


Author Portman, Katherine L.
Long, Jed
Carr, Stephen
Briand, Loic
Winzor, Donald J.
Searle, Mark S.
Scott, David J.
Title Enthalpy/entropy compensation effects from cavity desolvation underpin broad ligand binding selectivity for rat odorant binding protein 3
Journal name Biochemistry   Check publisher's open access policy
ISSN 1520-4995
0006-2960
Publication date 2014-04-15
Year available 2014
Sub-type Article (original research)
DOI 10.1021/bi5002344
Open Access Status
Volume 53
Issue 14
Start page 2371
End page 2379
Total pages 9
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2015
Language eng
Abstract Evolution has produced proteins with exquisite ligand binding specificity, and manipulating this effect has been the basis for much of modern rational drug design. However, there are general classes of proteins with broader ligand selectivity linked to function, the origin of which is poorly understood. The odorant binding proteins (OBPs) sequester volatile molecules for transportation to the olfactory receptors. Rat OBP3, which we characterize by X-ray crystallography and NMR, binds a homologous series of aliphatic γ-lactones within its aromatic-rich hydrophobic pocket with remarkably little variation in affinity but extensive enthalpy/entropy compensation effects. We show that the binding energetics are modulated by two desolvation processes with quite different thermodynamic signatures. Ligand desolvation follows the classical hydrophobic effect; however, cavity desolvation is consistent with the liberation of "high energy" water molecules back into bulk solvent with a strong, but compensated, enthalpic contribution, which together underpin the origins of broad ligand binding selectivity.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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