Genetic studies of protein stability and mechanisms of folding.
In the past few years, analysis of mutationally altered proteins has joined more traditional biophysical methods as an important experimental approach to the study of protein folding. Single amino acid substitutions have been found to reduce the stability of the native state by as much as 3 kcal mol-1, a significant fraction of the marginal stability of the folded conformation, and to significantly alter the rates of folding or unfolding. Mutations can also significantly affect the ability of a protein to fold in vivo. However, at present there is great uncertainty in accounting for or predicting the effects of mutations on stability and folding, even qualitatively. Future studies of mutant proteins are likely to provide further insights into the roles of individual residues and interactions in determining the three-dimensional structures of proteins. For the full potential of this approach to be realized, however, many mutant proteins will have to be systematically studied using structural, thermodynamic, and kinetic methods. The results of these experiments may aid in developing and refining improved theoretical treatments of the energetics of protein conformation.
Goldenberg
D P
DP
Department of Biology, University of Utah, Salt Lake City 84112.
D004355:Drug Stability; D004795:Enzyme Stability; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
D004798:Enzymes; D011506:Proteins