Enthalpy of hydrogen bond formation in aprotein-ligand binding reaction.
Open Access
- 1 March 1994
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (5), 1964-1968
- https://doi.org/10.1073/pnas.91.5.1964
Abstract
Parallel measurements of the thermodynamics (free-energy, enthalpy, entropy and heat-capacity changes) of ligand binding to FK506 binding protein (FKBP-12) in H2O and D2O have been performed in an effort to probe the energetic contributions of single protein-ligand hydrogen bonds formed in the binding reactions. Changing tyrosine-82 to phenylalanine in FKBP-12 abolishes protein-ligand hydrogen bond interactions in the FKBP-12 complexes with tacrolimus or rapamycin and leads to a large apparent enthalpic stabilization of binding in both H2O and D2O. High-resolution crystallographic analysis reveals that two water molecules bound to the tyrosine-82 hydroxyl group in unliganded FKBP-12 are displaced upon formation of the protein-ligand complexes. A thermodynamic analysis is presented that suggests that the removal of polar atoms from water contributes a highly unfavorable enthalpy change to the formation of C=O...HO hydrogen bonds as they occur in the processes of protein folding and ligand binding. Despite the less favorable enthalpy change, the entropic advantage of displacing two water molecules upon binding leads to a slightly more favorable free-energy change of binding in the reactions with wild-type FKBP-12.Keywords
This publication has 20 references indexed in Scilit:
- Probing hydration contributions to the thermodynamics of ligand binding by proteins. Enthalpy and heat capacity changes of tacrolimus and rapamycin binding to FK506 binding protein in deuterium oxide and waterBiochemistry, 1993
- Estimation of the maximum change in stability of globular proteins upon mutation of a hydrophobic residue to another of smaller sizeProtein Science, 1993
- Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and RapamycinJournal of Molecular Biology, 1993
- Analysis of the heat capacity dependence of protein foldingJournal of Molecular Biology, 1992
- Contribution of the hydrophobic effect to globular protein stabilityJournal of Molecular Biology, 1992
- Use of liquid hydrocarbon and amide transfer data to estimate contributions to thermodynamic functions of protein folding from the removal of nonpolar and polar surface from waterBiochemistry, 1992
- Contribution of hydrogen bonding to the conformational stability of ribonuclease T1Biochemistry, 1992
- Solid model compounds and the thermodynamics of protein unfoldingJournal of Molecular Biology, 1991
- Solution structure of the major binding protein for the immunosuppressant FK506Nature, 1991
- Hydrogen bonding in globular proteinsProgress in Biophysics and Molecular Biology, 1984