Inactivation of mesotrypsin by chymotrypsin C prevents trypsin inhibitor degradation.


Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
13 03 2020
Historique:
received: 03 01 2020
pubmed: 6 2 2020
medline: 15 12 2020
entrez: 5 2 2020
Statut: ppublish

Résumé

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

Identifiants

pubmed: 32014997
pii: S0021-9258(17)48617-0
doi: 10.1074/jbc.RA120.012526
pmc: PMC7076226
pii:
doi:

Substances chimiques

Caseins 0
SPINK1 protein, human 0
Trypsin Inhibitors 0
Trypsin Inhibitor, Kazal Pancreatic 50936-63-5
Chymotrypsin EC 3.4.21.1
chymotrypsin C EC 3.4.21.2
PRSS3 protein, human EC 3.4.21.4
Trypsin EC 3.4.21.4

Banques de données

PDB
['2R9P']

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3447-3455

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK058088
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK082412
Pays : United States

Informations de copyright

© 2020 Toldi et al.

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Auteurs

Vanda Toldi (V)

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

András Szabó (A)

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Department of Molecular and Cell Biology, Center for Exocrine Disorders, Boston University, Henry M. Goldman School of Dental Medicine, Boston, Massachusetts 02118. Electronic address: andrasszabo@med.unideb.hu.

Miklós Sahin-Tóth (M)

Department of Molecular and Cell Biology, Center for Exocrine Disorders, Boston University, Henry M. Goldman School of Dental Medicine, Boston, Massachusetts 02118; Department of Surgery, University of California Los Angeles, Los Angeles, California 90095. Electronic address: msahintoth@mednet.ucla.edu.

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Classifications MeSH