2ato: Difference between revisions

Revision as of 19:27, 3 May 2008

Crystal structure of Human Cathepsin K in complex with myocrisin

OverviewOverview

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.

About this StructureAbout this Structure

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

ReferenceReference

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 Page seeded by OCA on Sat May 3 19:27:47 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2ato.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2ato |SIZE=350|CAPTION= <scene name='initialview01'>2ato</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_2ato", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=MYQ:(S)-(1,2-DICARBOXYETHYLTHIO)GOLD'>MYQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2ato|  PDB=2ato  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ato FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ato OCA], [http://www.ebi.ac.uk/pdbsum/2ato PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ato RCSB]</span>
-}}
 '''Crystal structure of Human Cathepsin K in complex with myocrisin'''
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 [[Category: Weidauer, E.]]
 [[Category: Yasuda, Y.]]
-[[Category: cathepsin k]]
+[[Category: Cathepsin k]]
-[[Category: myocrysin]]
+[[Category: Myocrysin]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 19:27:47 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:57:09 2008''