Determinants of chymotrypsin C cleavage specificity in the calcium-binding loop of human cationic trypsinogen.

ABSTRACT: The pancreatic serine protease chymotrypsin C (CTRC) cleaves the Leu81-Glu82 peptide bond in the calcium-binding loop of human cationic trypsinogen and thereby promotes its degradation. This serves as a protective mechanism against ectopic trypsinogen activation in the pancreas. In the present study, we demonstrate that cleavage of the Leu81-Glu82 peptide bond by CTRC is highly specific, and other human pancreatic chymotrypsins (CTRB1, CTRB2 and CTRL1) and elastases (ELA2A, ELA3A and ELA3B) do not catalyze this reaction. To elucidate the mechanistic basis for CTRC specificity, we surveyed the primary (P1) cleavage preference of these pancreatic proteases on peptide substrates. We found that CTRC cleaved after a P1 Leu with at least tenfold higher catalytic efficiency than other enzymes tes

SUBMITTER: Szabo A 

PROVIDER: S-EPMC3573857 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature