1YP7

Van der Waals Interactions Dominate Hydrophobic Association in a Protein Binding Site Occluded From Solvent Water

1YP7 の概要

• エントリーDOI: 10.2210/pdb1yp7/pdb
• 関連するPDBエントリー: 1YP6
• 分子名称: MAJOR URINARY PROTEIN 1, CADMIUM ION (3 entities in total)
• 機能のキーワード: lipocalin; beta-barrel; mup1; 2-methoxy-3-isobutylpyrazine, ligand binding protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Secreted: P11588
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20460.63

構造登録者

Barratt, E.,Bingham, R.J.,Warner, D.J.,Laughton, C.A.,Phillips, S.E.V.,Homans, S.W. (登録日: 2005-01-30, 公開日: 2005-08-30, 最終更新日: 2024-11-20)

主引用文献

Barratt, E.,Bingham, R.J.,Warner, D.J.,Laughton, C.A.,Phillips, S.E.V.,Homans, S.W.
Van der Waals Interactions Dominate Ligand-Protein Association in a Protein Binding Site Occluded from Solvent Water
J.Am.Chem.Soc., 127:11827-11834, 2005

PubMed Abstract: In the present study we examine the enthalpy of binding of 2-methoxy-3-isobutylpyrazine (IBMP) to the mouse major urinary protein (MUP), using a combination of isothermal titration calorimetry (ITC), NMR, X-ray crystallography, all-atom molecular dynamics simulations, and site-directed mutagenesis. Global thermodynamics data derived from ITC indicate that binding is driven by favorable enthalpic contributions, rather than a classical entropy-driven signature that might be expected given that the binding pocket of MUP-1 is very hydrophobic. The only ligand-protein hydrogen bond is formed between the side-chain hydroxyl of Tyr120 and the ring nitrogen of the ligand in the wild-type protein. ITC measurements on the binding of IBMP to the Y120F mutant demonstrate a reduced enthalpy of binding, but nonetheless binding is still enthalpy dominated. A combination of solvent isotopic substitution ITC measurements and all-atom molecular dynamics simulations with explicit inclusion of solvent water suggests that solvation is not a major contributor to the overall binding enthalpy. Moreover, hydrogen/deuterium exchange measurements suggest that there is no significant contribution to the enthalpy of binding derived from "tightening" of the protein structure. Data are consistent with binding thermodynamics dominated by favorable dispersion interactions, arising from the inequality of solvent-solute dispersion interactions before complexation versus solute-solute dispersion interactions after complexation, by virtue of poor solvation of the binding pocket.

PubMed: 16104761
DOI: 10.1021/ja0527525

実験手法

X-RAY DIFFRACTION (2 Å)