2ato

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[[Image:2ato.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_2ato| PDB=2ato | SCENE= }}
{{STRUCTURE_2ato| PDB=2ato | SCENE= }}
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'''Crystal structure of Human Cathepsin K in complex with myocrisin'''
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===Crystal structure of Human Cathepsin K in complex with myocrisin===
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==Overview==
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Rheumatoid arthritis is an inflammatory and disabling joint disease affecting 0.5-1.5% of the population. Although various anti-inflammatory (NSAIDs) and disease-modifying (DMARDs) drugs are in clinical use, their precise mechanisms of action are not always defined. In this report, we discuss the effects of widely used DMARDs such as gold derivatives and chloroquine on cathepsins K and S, which have been implicated as critical mediators of inflammation and joint erosion in rheumatoid arthritis. We demonstrate that clinically potent gold derivatives inhibit cathepsins K and S in in vitro and cell-based assays. An X-ray analysis of the gold thiomalate/cathepsin K complex reveals that the inhibitor is bound to the active-site cysteine residue of the protease. Chloroquine, a lysosomotropic agent of lower clinical potency than gold derivatives, inhibits neutral pH-labile cathepsins intracellularly, but does not affect the neutral pH-stable cathepsin S. The potent inhibition of cathepsins implicated in the pathogenesis of rheumatoid arthritis by gold derivatives may explain the therapeutic efficacy of these drugs.
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The line below this paragraph, {{ABSTRACT_PUBMED_17338641}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 17338641 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17338641}}
==About this Structure==
==About this Structure==
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[[Category: Cathepsin k]]
[[Category: Cathepsin k]]
[[Category: Myocrysin]]
[[Category: Myocrysin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:27:47 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:44:47 2008''

Revision as of 15:44, 27 July 2008

Image:2ato.png

Template:STRUCTURE 2ato

Crystal structure of Human Cathepsin K in complex with myocrisin

Template:ABSTRACT PUBMED 17338641

About this Structure

2ATO is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S., Weidauer E, Yasuda Y, Biswal BK, Cherny M, James MN, Bromme D, Biol Chem. 2007 Mar;388(3):331-6. PMID:17338641

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