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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2000-11-28
pubmed:abstractText
The prodomains of several cysteine proteases of the papain family have been shown to be potent inhibitors of their parent enzymes. An increased interest in cysteine proteases inhibitors has been generated with potential therapeutic targets such as cathepsin K for osteoporosis and cathepsin S for immune modulation. The propeptides of cathepsin S, L and K were expressed as glutathione S-transferase-fusion proteins in Escherichia coli. The proteins were purified on glutathione affinity columns and the glutathione S-transferase was removed by thrombin cleavage. All three propeptides were tested for inhibitor potency and found to be selective within the cathepsin L subfamily (cathepsins K, L and S) compared with cathepsin B or papain. Inhibition of cathepsin K by either procathepsin K, L or S was time-dependent and occurred by an apparent one-step mechanism. The cathepsin K propeptide had a Ki of 3.6-6.3 nM for each of the three cathepsins K, L and S. The cathepsin L propeptide was at least a 240-fold selective inhibitor of cathepsin K (Ki = 0.27 nM) and cathepsin L (Ki = 0.12 nM) compared with cathepsin S (Ki = 65 nM). Interestingly, the cathepsin S propeptide was more selective for inhibition of cathepsin L (Ki = 0.46 nM) than cathepsin S (Ki = 7.6 nM) itself or cathepsin K (Ki = 7.0 nM). This is in sharp contrast to previously published data demonstrating that the cathepsin S propeptide is equipotent for inhibition of human cathepsin S and rat and paramecium cathepsin L [Maubach, G., Schilling, K., Rommerskirch, W., Wenz, I., Schultz, J. E., Weber, E. & Wiederanders, B. (1997), Eur J. Biochem. 250, 745-750]. These results demonstrate that limited selectivity of inhibition can be measured for the procathepsins K, L and S vs. the parent enzymes, but selective inhibition vs. cathepsin B and papain was obtained.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CTSK protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CTSL1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin K, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin L, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins, http://linkedlifedata.com/resource/pubmed/chemical/Ctsk protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Ctsl protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Papain, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/cathepsin S
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6311-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11012686-Amino Acid Sequence, pubmed-meshheading:11012686-Animals, pubmed-meshheading:11012686-Cathepsin K, pubmed-meshheading:11012686-Cathepsin L, pubmed-meshheading:11012686-Cathepsins, pubmed-meshheading:11012686-Cloning, Molecular, pubmed-meshheading:11012686-Cysteine Endopeptidases, pubmed-meshheading:11012686-Cysteine Proteinase Inhibitors, pubmed-meshheading:11012686-Endopeptidases, pubmed-meshheading:11012686-Enzyme Precursors, pubmed-meshheading:11012686-Escherichia coli, pubmed-meshheading:11012686-Humans, pubmed-meshheading:11012686-Kinetics, pubmed-meshheading:11012686-Molecular Sequence Data, pubmed-meshheading:11012686-Papain, pubmed-meshheading:11012686-Rats, pubmed-meshheading:11012686-Recombinant Proteins, pubmed-meshheading:11012686-Sequence Alignment, pubmed-meshheading:11012686-Sequence Homology, Amino Acid
pubmed:year
2000
pubmed:articleTitle
Potency and selectivity of inhibition of cathepsin K, L and S by their respective propeptides.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada.
pubmed:publicationType
Journal Article