Zymogen activation confers thermodynamic stability on a key peptide bond and protects human cationic trypsin from degradation

Abstract

Background: Initial cleavage by chymotrypsin C regulates degradation of human cationic trypsin. Results: Cleavage is reversible and favors calcium-dependent bond formation in trypsin, but not in trypsinogen. Conclusion: Trypsin resistance to degradation derives from the regulated thermodynamic stability of a specific peptide bond that is responsive to physiological environment. Significance: This new paradigm explains the robustness of trypsin functioning in the protease-rich intestinal milieu. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.