Inactivation of mesotrypsin by chymotrypsin C prevents trypsin inhibitor degradation.

ABSTRACT: Mesotrypsin is an unusual human trypsin isoform with inhibitor resistance and the ability to degrade trypsin inhibitors. Degradation of the protective serine protease inhibitor Kazal type 1 (SPINK1) by mesotrypsin in the pancreas may contribute to the pathogenesis of pancreatitis. Here we tested the hypothesis that the regulatory digestive protease chymotrypsin C (CTRC) mitigates the harmful effects of mesotrypsin by cleaving the autolysis loop. As human trypsins are post-translationally sulfated in the autolysis loop, we also assessed the effect of this modification. We found that mesotrypsin cleaved in the autolysis loop by CTRC exhibited catalytic impairment on short peptides due to a 10-fold increase in K_m , it digested β-casein poorly and bound soybean trypsin inhibi

SUBMITTER: Toldi V 

PROVIDER: S-EPMC7076226 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature