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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1999-9-23
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pubmed:abstractText |
Cathepsin K is a cysteine protease involved in degradation of human type I collagen and plays a primary role in bone resorption. We have cloned rhesus monkey cathepsin K by reverse transcriptase-polymerase chain reaction (RT-PCR) from rhesus ovary poly A+ RNA. The sequence for the rhesus enzyme is 98% identical to that of the human with 100% identity within the mature active form of cathepsin K. Rhesus monkey cathepsin K was transiently expressed in Chinese hamster ovary (CHO) cells and found to be secreted as the proenzyme in the culture media and 50% activated to the mature form intracellularly. The substrate specificity preference of aminomethylcoumarin and rhodamine peptide substrates was Leu > Phe > Pro in the P2 position when tested with constant arginine at P1. The enzyme activity expressed in CHO cell extracts was sensitive to inhibition by E-64 and cystatin with IC50s of 3.5 nmol/L and 13 ng/mL, respectively. The apparent second order rate constants of inactivation by E-64 were 66,000 M(-1) s(-1) and 130,000 M(-1) s(-1) for the recombinantly expressed rhesus monkey and human cathepsin K, respectively. The high similarity between the sequences and the kinetic properties of rhesus monkey and human cathepsin K establishes this monkey species as a suitable animal model for development of novel cathepsin K inhibitors as antiresorptive agents.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ac-aspartyl-glutamyl-valyl-aspartyl-...,
http://linkedlifedata.com/resource/pubmed/chemical/CTSK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin K,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Coumarins,
http://linkedlifedata.com/resource/pubmed/chemical/Cystatins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/E 64,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Polynucleotide Adenylyltransferase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
8756-3282
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
205-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10456386-Amino Acid Sequence,
pubmed-meshheading:10456386-Animals,
pubmed-meshheading:10456386-CHO Cells,
pubmed-meshheading:10456386-Cathepsin K,
pubmed-meshheading:10456386-Cathepsins,
pubmed-meshheading:10456386-Cloning, Molecular,
pubmed-meshheading:10456386-Coumarins,
pubmed-meshheading:10456386-Cricetinae,
pubmed-meshheading:10456386-Cystatins,
pubmed-meshheading:10456386-DNA, Complementary,
pubmed-meshheading:10456386-DNA Primers,
pubmed-meshheading:10456386-Enzyme Inhibitors,
pubmed-meshheading:10456386-Enzyme Precursors,
pubmed-meshheading:10456386-Female,
pubmed-meshheading:10456386-Gene Expression,
pubmed-meshheading:10456386-Humans,
pubmed-meshheading:10456386-Leucine,
pubmed-meshheading:10456386-Macaca mulatta,
pubmed-meshheading:10456386-Molecular Sequence Data,
pubmed-meshheading:10456386-Oligopeptides,
pubmed-meshheading:10456386-Peptide Fragments,
pubmed-meshheading:10456386-Polynucleotide Adenylyltransferase,
pubmed-meshheading:10456386-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10456386-Sequence Homology, Amino Acid,
pubmed-meshheading:10456386-Substrate Specificity
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pubmed:year |
1999
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pubmed:articleTitle |
Cloning and expression of rhesus monkey cathepsin K.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study
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