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3kw9

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'''Unreleased structure'''
 
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The entry 3kw9 is ON HOLD
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==X-ray structure of Cathepsin K covalently bound to a triazine ligand==
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<StructureSection load='3kw9' size='340' side='right' caption='[[3kw9]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3kw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KW9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ORG:4-(CYCLOHEXYLAMINO)-6-PIPERAZIN-1-YL-1,3,5-TRIAZINE-2-CARBONITRILE'>ORG</scene>, <scene name='pdbligand=TFA:TRIFLUOROACETIC+ACID'>TFA</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kwb|3kwb]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kw9 OCA], [http://pdbe.org/3kw9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3kw9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kw9 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN]] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[http://omim.org/entry/265800 265800]]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.<ref>PMID:8703060</ref> <ref>PMID:9529353</ref> <ref>PMID:10491211</ref> <ref>PMID:10878663</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN]] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kw/3kw9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kw9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Morphing structural features of HTS-derived chemotypes led to the discovery of novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic profiles, for example, compound 20 showed high catK potency (IC(50)=4nM), &gt;580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%.
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Authors: Uitdehaag, J.C.M., van Zeeland, M.
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Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors.,Rankovic Z, Cai J, Kerr J, Fradera X, Robinson J, Mistry A, Hamilton E, McGarry G, Andrews F, Caulfield W, Cumming I, Dempster M, Waller J, Scullion P, Martin I, Mitchell A, Long C, Baugh M, Westwood P, Kinghorn E, Bruin J, Hamilton W, Uitdehaag J, van Zeeland M, Potin D, Saniere L, Fouquet A, Chevallier F, Deronzier H, Dorleans C, Nicolai E Bioorg Med Chem Lett. 2010 Mar 1;20(5):1524-7. Epub 2010 Jan 25. PMID:20149657<ref>PMID:20149657</ref>
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Description: X-ray structure of Cathepsin K covalently bound to a triazine ligand
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 30 13:47:34 2009''
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<div class="pdbe-citations 3kw9" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Cathepsin K]]
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[[Category: Human]]
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[[Category: Uitdehaag, J C.M]]
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[[Category: Zeeland, M van]]
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[[Category: Cys protease]]
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[[Category: Cysteine]]
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[[Category: Disulfide bond]]
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[[Category: Hydrolase]]
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[[Category: Inhibitor]]
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[[Category: Non-peptide]]
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[[Category: Protease]]
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[[Category: Thioimidate]]
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[[Category: Thiol protease]]
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[[Category: Zymogen]]

Current revision

X-ray structure of Cathepsin K covalently bound to a triazine ligand

3kw9, resolution 1.80Å

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