 |
PDBsum entry 1qy1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transport protein
|
PDB id
|
|
|
|
1qy1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Thermodynamics of binding of 2-Methoxy-3-Isopropylpyrazine and 2-Methoxy-3-Isobutylpyrazine to the major urinary protein.
|
|
|
Authors
|
|
R.J.Bingham,
J.B.Findlay,
S.Y.Hsieh,
A.P.Kalverda,
A.Kjellberg,
C.Perazzolo,
S.E.Phillips,
K.Seshadri,
C.H.Trinh,
W.B.Turnbull,
G.Bodenhausen,
S.W.Homans.
|
|
|
Ref.
|
|
J Am Chem Soc, 2004,
126,
1675-1681.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
In the present study we examine the thermodynamics of binding of two related
pyrazine-derived ligands to the major urinary protein, MUP-I, using a
combination of isothermal titration calorimetry (ITC), X-ray crystallography,
and NMR backbone (15)N and methyl side-chain (2)H relaxation measurements.
Global thermodynamics data derived from ITC indicate that binding is driven by
favorable enthalpic contributions, rather than the classical entropy-driven
hydrophobic effect. Unfavorable entropic contributions from the protein backbone
and side-chain residues in the vicinity of the binding pocket are partially
offset by favorable entropic contributions at adjacent positions, suggesting a
"conformational relay" mechanism whereby increased rigidity of residues on
ligand binding are accompanied by increased conformational freedom of side
chains in adjacent positions. The principal driving force governing ligand
affinity and specificity can be attributed to solvent-driven enthalpic effects
from desolvation of the protein binding pocket.
|
|
|
|
|
|
|
