3ZQ3

Crystal Structure of Rat Odorant Binding Protein 3 (OBP3)

Summary for 3ZQ3

• Entry DOI: 10.2210/pdb3zq3/pdb
• Descriptor: OBP3 PROTEIN (1 entity in total)
• Functional Keywords: odorant binding protein, lipocalin, enthalpy-entropy
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Total number of polymer chains: 4
• Total formula weight: 79756.98

Authors

Portman, K.L.,Long, J.,Carr, S.,Brand, L.,Winzor, D.J.,Searle, M.,Scott, D.J. (deposition date: 2013-03-05, release date: 2014-03-12, Last modification date: 2024-11-20)

Primary citation

Portman, K.L.,Long, J.,Carr, S.,Briand, L.,Winzor, D.J.,Searle, M.S.,Scott, D.J.
Enthalpy/Entropy Compensation Effects from Cavity Desolvation Underpin Broad Ligand Binding Selectivity for Rat Odorant Binding Protein 3
Biochemistry, 53:2371-, 2014

PubMed 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.

PubMed: 24665925
DOI: 10.1021/BI5002344

Experimental method

X-RAY DIFFRACTION (2.8 Å)