2DM5
Thermodynamic Penalty Arising From Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor
Summary for 2DM5
| Entry DOI | 10.2210/pdb2dm5/pdb |
| Descriptor | Major Urinary Protein, CADMIUM ION, OCTANE-1,8-DIOL, ... (4 entities in total) |
| Functional Keywords | beta barrel, lipocalin, transport protein |
| Biological source | Mus musculus (house mouse) |
| Cellular location | Secreted: P11589 |
| Total number of polymer chains | 1 |
| Total formula weight | 20735.27 |
| Authors | Barratt, E.,Bronowska, A.,Vondrasek, J.,Bingham, R.,Phillips, S.,Homans, S.W. (deposition date: 2006-04-20, release date: 2006-10-17, Last modification date: 2024-10-23) |
| Primary citation | Barratt, E.,Bronowska, A.,Vondrasek, J.,Cerny, J.,Bingham, R.,Phillips, S.,Homans, S.W. Thermodynamic penalty arising from burial of a ligand polar group within a hydrophobic pocket of a protein receptor J.Mol.Biol., 362:994-1003, 2006 Cited by PubMed Abstract: Here, we examine the thermodynamic penalty arising from burial of a polar group in a hydrophobic pocket that forms part of the binding-site of the major urinary protein (MUP-I). X-ray crystal structures of the complexes of octanol, nonanol and 1,8 octan-diol indicate that these ligands bind with similar orientations in the binding pocket. Each complex is characterised by a bridging water molecule between the hydroxyl group of Tyr120 and the hydroxyl group of each ligand. The additional hydroxyl group of 1,8 octan-diol is thereby forced to reside in a hydrophobic pocket, and isothermal titration calorimetry experiments indicate that this is accompanied by a standard free energy penalty of +21 kJ/mol with respect to octanol and +18 kJ/mol with respect to nonanol. Consideration of the solvation thermodynamics of each ligand enables the "intrinsic" (solute-solute) interaction energy to be determined, which indicates a favourable enthalpic component and an entropic component that is small or zero. These data indicate that the thermodynamic penalty to binding derived from the unfavourable desolvation of 1,8 octan-diol is partially offset by a favourable intrinsic contribution. Quantum chemical calculations suggest that this latter contribution derives from favourable solute-solute dispersion interactions. PubMed: 16935302DOI: 10.1016/j.jmb.2006.07.067 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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