Disulfide Interchange and the Three-Dimensional Structure of Proteins

This article was published after Anfinsen's laboratory had delineated and demonstrated the major principles of protein folding and during a period when research at the lab turned to the disulfide interchange enzyme that accelerates the reactivation of the reduced form of ribonuclease. In the lab, Givol and Goldberger had worked to achieve in vitro the reactivation rates that would be compatible with the rate of protein biosynthesis. Purifying the enzyme proved difficult, so the team decided to utilize disulfide interchange activity to demonstrate other aspects related to protein folding and structure. The results of these experiments were consistent with the idea that the disulfide bonds in chymtrypsinogen were formed according to the information present in the single-chain protein, which is subsequently converted by peptide bond cleavage to the metastable three-chain chymotrypsin. Based on this, Anfinsen's group reasoned that the inactivation of a multi-chain protein by disulfide interchange indicated its origin as a single-chain protein during biosynthesis.