Protein energy landscapes determined by five-dimensional crystallography
نویسندگان
چکیده
Free-energy landscapes decisively determine the progress of enzymatically catalyzed reactions [Cornish-Bowden (2012), Fundamentals of Enzyme Kinetics, 4th ed.]. Time-resolved macromolecular crystallography unifies transient-state kinetics with structure determination [Moffat (2001), Chem. Rev. 101, 1569-1581; Schmidt et al. (2005), Methods Mol. Biol. 305, 115-154; Schmidt (2008), Ultrashort Laser Pulses in Medicine and Biology] because both can be determined from the same set of X-ray data. Here, it is demonstrated how barriers of activation can be determined solely from five-dimensional crystallography, where in addition to space and time, temperature is a variable as well [Schmidt et al. (2010), Acta Cryst. A66, 198-206]. Directly linking molecular structures with barriers of activation between them allows insight into the structural nature of the barrier to be gained. Comprehensive time series of crystallographic data at 14 different temperature settings were analyzed and the entropy and enthalpy contributions to the barriers of activation were determined. One hundred years after the discovery of X-ray scattering, these results advance X-ray structure determination to a new frontier: the determination of energy landscapes.
منابع مشابه
Protein Energy Landscapes Determined by 5-Dimensional Crystallography
Free energy landscapes decisively determine the progress of enzymatically catalyzed reactions. Timeresolved macromolecular crystallography unifies transient-state kinetics with structure determination because both can be determined from the same set of X-ray data. We demonstrate here how barriers of activation can be determined solely from five-dimensional crystallography. Directly linking mole...
متن کاملPredicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins.
A simple and fast free energy scoring function (Fresno) has been developed to predict the binding free energy of peptides to class I major histocompatibility (MHC) proteins. It differs from existing scoring functions mainly by the explicit treatment of ligand desolvation and of unfavorable protein-ligand contacts. Thus, it may be particularly useful in predicting binding affinities from three-d...
متن کاملIdentification of RNA-binding sites in artemin based on docking energy landscapes and molecular dynamics simulation
There are questions concerning the functions of artemin, an abundant stress protein found in Artemiaduring embryo development. It has been reported that artemin binds RNA at high temperatures in vitro, suggesting an RNA protective role. In this study, we investigated the possibility of the presence of RNA-bindingsites and their structural properties in artemin, using docking energy ...
متن کاملAlternate states of proteins revealed by detailed energy landscape mapping.
What conformations do protein molecules populate in solution? Crystallography provides a high-resolution description of protein structure in the crystal environment, while NMR describes structure in solution but using less data. NMR structures display more variability, but is this because crystal contacts are absent or because of fewer data constraints? Here we report unexpected insight into th...
متن کاملThe crystal structure of a mutant human lysozyme C77/95A with increased secretion efficiency in yeast.
The three-dimensional structure of a mutant human lysozyme, C77/95A, in which residues Cys77 and Cys95 were replaced by alanine, was determined at 1.8-A resolution by x-ray crystallography. The properties of this mutant protein have been well characterized with respect to its thermal stability and secretion efficiency in a yeast expression system. The overall three-dimensional structure of C77/...
متن کامل