title: A kinetic explanation for the rearrangement pathway of BPTI folding.
abstract: Bovine pancreatic trypsin inhibitor (BPTI) does not fold by simple sequential formation of its native disulphide bonds. Instead, an initially formed intermediate, termed N', first rearranges to a more stable species in a slow process that requires substantial unfolding. We find that direct oxidation of N' is also inhibited by native structure which slows both the intermolecular step in oxidation--formation of a mixed disulphide bond with the oxidizing agent GSSG--as well as the subsequent intramolecular step. Folding does not occur appreciably by direct oxidation because the high GSSG concentrations required for efficient mixed disulphide formation cause N' to accumulate as a nonproductive, double-mixed disulphide species. The need to unfold previously acquired native structure, observed in the folding of BPTI, may be a common feature of disulphide-linked folding reactions.
authors.affiliation: Howard Hughes Medical Institute, Department of Physics, M.I.T. Nine Cambridge Center, Massachusetts 02142, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Weissman
authors.forename: P S
authors.initials: PS
authors.lastname: Kim
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000737:chemistry*; D002417:Cattle; D004220:Disulfides / Q000737:chemistry; D007700:Kinetics; D010084:Oxidation-Reduction; D017510:Protein Folding; D013696:Temperature
chemical_list: D004220:Disulfides; D007611:Aprotinin