Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B.

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dc.contributor.author Sripa, J
dc.contributor.author Laha, T
dc.contributor.author To, J
dc.contributor.author Brindley, PJ
dc.contributor.author Sripa, B
dc.contributor.author Kaewkes, S
dc.contributor.author Dalton, JP
dc.contributor.author Robinson, MW
dc.date.accessioned 2011-02-07T06:25:04Z
dc.date.issued 2010-06
dc.identifier.citation Cellular microbiology, 2010, 12 (6), pp. 781 - 795
dc.identifier.issn 1462-5814
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/13830
dc.description.abstract Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that autocatalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot autocatalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma.
dc.format Print-Electronic
dc.language eng
dc.relation.hasversion Accepted manuscript version en_US
dc.relation.isbasedon 10.1111/j.1462-5822.2010.01433.x
dc.title Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B.
dc.type Journal Article
dc.parent Cellular microbiology
dc.journal.volume 6
dc.journal.volume 12
dc.journal.number 6 en_US
dc.publocation Singapore en_US
dc.identifier.startpage 781 en_US
dc.identifier.endpage 795 en_US
dc.cauo.name SCI.Institute for Biotechnology of Infectious Diseases en_US
dc.conference Verified OK en_US
dc.for 0605 Microbiology
dc.personcode 030896
dc.personcode 100777
dc.personcode 030199
dc.percentage 100 en_US
dc.classification.name Microbiology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.location.activity WOS:000288274500008
dc.description.keywords Animals
dc.description.keywords Opisthorchis
dc.description.keywords Cathepsin B
dc.description.keywords Extracellular Matrix Proteins
dc.description.keywords DNA, Helminth
dc.description.keywords Helminth Proteins
dc.description.keywords Sequence Analysis, DNA
dc.description.keywords Protein Structure, Tertiary
dc.description.keywords Gene Expression Regulation
dc.description.keywords Protein Processing, Post-Translational
dc.description.keywords Amino Acid Sequence
dc.description.keywords Molecular Sequence Data
dc.description.keywords Cathepsin F
dc.description.keywords Hydrogen-Ion Concentration
dc.description.keywords Models, Molecular
dc.description.keywords Hemoglobins
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
utslib.copyright.status Open Access
utslib.copyright.date 2015-04-15 12:23:47.074767+10
pubs.consider-herdc true
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)
utslib.collection.history General (ID: 2)


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