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2dm5
From Proteopedia
(New page: 200px<br /><applet load="2dm5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dm5, resolution 1.7Å" /> '''Thermodynamic Penalty...) |
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| - | [[Image:2dm5.gif|left|200px]]<br /><applet load="2dm5" size=" | + | [[Image:2dm5.gif|left|200px]]<br /><applet load="2dm5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2dm5, resolution 1.7Å" /> | caption="2dm5, resolution 1.7Å" /> | ||
'''Thermodynamic Penalty Arising From Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor'''<br /> | '''Thermodynamic Penalty Arising From Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Here, we examine the thermodynamic penalty arising from burial of a polar | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2DM5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CD and ODI as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2DM5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CD:'>CD</scene> and <scene name='pdbligand=ODI:'>ODI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DM5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bingham, R.]] | [[Category: Bingham, R.]] | ||
[[Category: Bronowska, A.]] | [[Category: Bronowska, A.]] | ||
| - | [[Category: Homans, S | + | [[Category: Homans, S W.]] |
[[Category: Phillips, S.]] | [[Category: Phillips, S.]] | ||
[[Category: Vondrasek, J.]] | [[Category: Vondrasek, J.]] | ||
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[[Category: lipocalin]] | [[Category: lipocalin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:00:14 2008'' |
Revision as of 15:00, 21 February 2008
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Thermodynamic Penalty Arising From Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor
Overview
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.
About this Structure
2DM5 is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Thermodynamic penalty arising from burial of a ligand polar group within a hydrophobic pocket of a protein receptor., Barratt E, Bronowska A, Vondrasek J, Cerny J, Bingham R, Phillips S, Homans SW, J Mol Biol. 2006 Oct 6;362(5):994-1003. Epub 2006 Aug 1. PMID:16935302
Page seeded by OCA on Thu Feb 21 17:00:14 2008
Categories: Mus musculus | Single protein | Barratt, E. | Bingham, R. | Bronowska, A. | Homans, S W. | Phillips, S. | Vondrasek, J. | CD | ODI | Beta barrel | Lipocalin
