Human Cationic Trypsinogen. the Tetra-aspartate Motif in the Activation Peptide Is Essential for Autoactivation Control, but Not for Enteropeptidase Recognition
نویسنده
چکیده
ACTIVATION PEPTIDE IS ESSENTIAL FOR AUTOACTIVATION CONTROL, BUT NOT FOR ENTEROPEPTIDASE RECOGNITION. Zsófia Nemoda and Miklós Sahin-Tóth From the Department of Molecular and Cell Biology, Boston University, Goldman School of Dental Medicine, Boston, MA, 02118 Running title: Trypsinogen activation peptide. Address correspondence to Miklós Sahin-Tóth, 715 Albany Street, Evans-433; Boston, MA 02118 Tel: (617) 414-1070; Fax: (617) 414-1041; E-mail: [email protected]
منابع مشابه
Evolution of trypsinogen activation peptides.
The activation peptide of mammalian trypsinogens contains a highly conserved tetra-aspartate sequence (D19-D20-D21-D22) preceding the K23-I24 scissile peptide bond, which is hydrolyzed as the first step in the activation process. Here, we examined the evolution and function of trypsinogen activation peptides through integrating functional characterization of disease-associated mutations with co...
متن کاملMUTATIONS OF THE TRYPSINOGEN ACTIVATION PEPTIDE IN HEREDITARY PANCREATITIS Ph.D. Thesis
independence and diminished secretion define a subset of hereditary pancreatitis associated cationic trypsinogen mutants. pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl − channels and luminal anion exchangers. Hegyi P. NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts. survival and the motor performance in a transgenic mouse...
متن کاملChymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen.
Trypsin-mediated trypsinogen activation (autoactivation) facilitates digestive zymogen activation in the duodenum but may precipitate pancreatitis if it occurs prematurely in the pancreas. Autoactivation of human cationic trypsinogen is inhibited by a repulsive electrostatic interaction between the unique Asp218 on the surface of cationic trypsin and the conserved tetra-aspartate (Asp19-22) mot...
متن کاملStructural Basis for the Specific Activation of Human Cationic Trypsinogen by Human Enteropeptidase”
Human cationic trypsinogen is activated by human enteropeptidase much more readily than bovine trypsinogen, the ratios k,,,/K,,, being 330 and 11 mr+-’ s’, respectively. Conversely, porcine enteropeptidase activates bovine trypsinoyen much more rapidly (k&K,,, = 630 rnM-‘s-‘) than human cationic trypsinogen (k,,,/K,,, = 2.4 mM-‘s--‘). The primary structure of the activation region of human cati...
متن کاملProtein surface charge of trypsinogen changes its activation pattern
BACKGROUND Trypsinogen is the inactive precursor of trypsin, a serine protease that cleaves proteins and peptides after arginine and lysine residues. In this study, human trypsinogen was used as a model protein to study the influence of electrostatic forces on protein-protein interactions. Trypsinogen is active only after its eight-amino-acid-long activation peptide has been cleaved off by anot...
متن کامل