2DM5

Thermodynamic Penalty Arising From Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor

2DM5 の概要

• エントリーDOI: 10.2210/pdb2dm5/pdb
• 分子名称: Major Urinary Protein, CADMIUM ION, OCTANE-1,8-DIOL, ... (4 entities in total)
• 機能のキーワード: beta barrel, lipocalin, transport protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Secreted: P11589
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20735.27

構造登録者

Barratt, E.,Bronowska, A.,Vondrasek, J.,Bingham, R.,Phillips, S.,Homans, S.W. (登録日: 2006-04-20, 公開日: 2006-10-17, 最終更新日: 2024-10-23)

主引用文献

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

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: 16935302
DOI: 10.1016/j.jmb.2006.07.067

実験手法

X-RAY DIFFRACTION (1.7 Å)