3kwb
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of CatK covalently bound to a dioxo-triazine inhibitor== | |
| + | <StructureSection load='3kwb' size='340' side='right'caption='[[3kwb]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3kwb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KWB FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ORH:3,5-DIOXO-4-(3-PIPERIDIN-1-YLPROPYL)-2-[3-(TRIFLUOROMETHYL)PHENYL]-2,3,4,5-TETRAHYDRO-1,2,4-TRIAZINE-6-CARBONITRILE'>ORH</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwb OCA], [https://pdbe.org/3kwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kwb RCSB], [https://www.ebi.ac.uk/pdbsum/3kwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kwb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[https://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> | ||
| + | == Function == | ||
| + | [https://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. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kw/3kwb_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=3kwb ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC(50) values of 17nM against catK and >10,000nM in catL, catB and catS assays. | ||
| - | + | Dioxo-triazines as a novel series of cathepsin K inhibitors.,Rankovic Z, Cai J, Fradera X, Dempster M, Mistry A, Mitchell A, Long C, Hamilton E, King A, Boucharens S, Jamieson C, Gillespie J, Cumming I, Uitdehaag J, van Zeeland M Bioorg Med Chem Lett. 2010 Mar 1;20(5):1488-90. Epub 2010 Jan 25. PMID:20153187<ref>PMID:20153187</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3kwb" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Cathepsin 3D structures|Cathepsin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Uitdehaag JCM]] | ||
| + | [[Category: Van Zeeland M]] | ||
Current revision
Structure of CatK covalently bound to a dioxo-triazine inhibitor
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