3kwz
From Proteopedia
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| - | {{STRUCTURE_3kwz| PDB=3kwz | SCENE= }} | ||
| - | ===Cathepsin K in complex with a non-selective 2-cyano-pyrimidine inhibitor=== | ||
| - | {{ABSTRACT_PUBMED_20149657}} | ||
| - | == | + | ==Cathepsin K in complex with a non-selective 2-cyano-pyrimidine inhibitor== |
| - | [[http://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN | + | <StructureSection load='3kwz' size='340' side='right'caption='[[3kwz]], [[Resolution|resolution]] 1.49Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3kwz]] is a 1 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=3KWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KWZ 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]] 1.49Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KWZ:4-(3-PIPERIDIN-1-YLPROPYL)-6-[3-(TRIFLUOROMETHYL)PHENYL]PYRIMIDINE-2-CARBONITRILE'>KWZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3kwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwz OCA], [https://pdbe.org/3kwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kwz RCSB], [https://www.ebi.ac.uk/pdbsum/3kwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kwz 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/3kwz_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=3kwz ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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), >580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%. | ||
| - | + | 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> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 3kwz" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Cathepsin|Cathepsin]] | + | *[[Cathepsin 3D structures|Cathepsin 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Fradera | + | [[Category: Large Structures]] |
| - | [[Category: Uitdehaag | + | [[Category: Fradera X]] |
| - | [[Category: Zeeland | + | [[Category: Uitdehaag JCM]] |
| - | + | [[Category: Van Zeeland M]] | |
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Current revision
Cathepsin K in complex with a non-selective 2-cyano-pyrimidine inhibitor
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