The renaturation of reduced polyalanyl-chymotrypsinogen and chymotrypsinogen.
Chymotrypsinogen has been successfully renatured in solution, after reduction of its 5 disulfide bonds in 6 M guanidine-HCl. This has been made possible by the study of the renaturation of a model derivative, polyalanyl-chymotrypsinogen. The reduced derivative is shown to refold and reoxodize spontaneously, with a 30-40% yield, into molecules which are monomeric and fully susceptible to activation by trypsin. Chymotrypsinogen can also be renatured but only in the presence of reagents allowing disulfide interchange and of moderate concentrations of guanidine-HCl or urea. These results illustrate how the kinetic trapping of incorrectly folded molecules by wrong S-S bonds and aggregation can be overcome, thus allowing the correct refolding of the protein.
D000409:Alanine; D001665:Binding Sites; D002919:Chymotrypsinogen; D005978:Glutathione; D006146:Guanidines; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010084:Oxidation-Reduction; D011119:Polynucleotides; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds; D014508:Urea
D006146:Guanidines; D011119:Polynucleotides; D013438:Sulfhydryl Compounds; D014508:Urea; D002919:Chymotrypsinogen; D005978:Glutathione; D000409:Alanine