3kx1: Difference between revisions

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<StructureSection load='3kx1' size='340' side='right'caption='[[3kx1]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
<StructureSection load='3kx1' size='340' side='right'caption='[[3kx1]], [[Resolution|resolution]] 1.51&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3kx1]] 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=3KX1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3KX1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3kx1]] 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=3KX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KX1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KX1:4-CYCLOHEPTYL-6-(3-PIPERIDIN-1-YLPROPYL)PYRIMIDINE-2-CARBONITRILE'>KX1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.51&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kwz|3kwz]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KX1:4-CYCLOHEPTYL-6-(3-PIPERIDIN-1-YLPROPYL)PYRIMIDINE-2-CARBONITRILE'>KX1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kx1 OCA], [https://pdbe.org/3kx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kx1 RCSB], [https://www.ebi.ac.uk/pdbsum/3kx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kx1 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3kx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kx1 OCA], [http://pdbe.org/3kx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kx1 RCSB], [http://www.ebi.ac.uk/pdbsum/3kx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kx1 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[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>
[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 ==
== Function ==
[[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.  
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=3kx1 ConSurf].
</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=3kx1 ConSurf].
<div style="clear:both"></div>
<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), &gt;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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3kx1" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cathepsin K]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Fradera, X]]
[[Category: Fradera X]]
[[Category: Uitdehaag, J C.M]]
[[Category: Uitdehaag JCM]]
[[Category: Zeeland, M van]]
[[Category: Van Zeeland M]]
[[Category: Cathepsin k]]
[[Category: Covalent reversible inhibitor]]
[[Category: Disease mutation]]
[[Category: Disulfide bond]]
[[Category: Enzyme inhibitor]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Lysosome]]
[[Category: Protease]]
[[Category: Thiol protease]]
[[Category: Zymogen]]

Revision as of 06:40, 3 April 2024

Cathepsin K in complex with a selective 2-cyano-pyrimidine inhibitor

3kx1, resolution 1.51Å

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