1yt7

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{{STRUCTURE_1yt7| PDB=1yt7 | SCENE= }}
 
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===Cathepsin K complexed with a constrained ketoamide inhibitor===
 
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{{ABSTRACT_PUBMED_15982880}}
 
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==Disease==
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==Cathepsin K complexed with a constrained ketoamide inhibitor==
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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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<StructureSection load='1yt7' size='340' side='right'caption='[[1yt7]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1yt7]] 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=1YT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YT7 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FC:(1R)-2,2-DIMETHYL-1-({5-[4-(TRIFLUOROMETHYL)PHENYL]-1,3,4-OXADIAZOL-2-YL}METHYL)PROPYL+(1S)-1-{OXO[(2-OXO-1,3-OXAZOLIDIN-3-YL)AMINO]ACETYL}PENTYLCARBAMATE'>3FC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yt7 OCA], [https://pdbe.org/1yt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yt7 RCSB], [https://www.ebi.ac.uk/pdbsum/1yt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yt7 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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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/yt/1yt7_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=1yt7 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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An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.
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==Function==
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P2-P3 conformationally constrained ketoamide-based inhibitors of cathepsin K.,Barrett DG, Boncek VM, Catalano JG, Deaton DN, Hassell AM, Jurgensen CH, Long ST, McFadyen RB, Miller AB, Miller LR, Payne JA, Ray JA, Samano V, Shewchuk LM, Tavares FX, Wells-Knecht KJ, Willard DH Jr, Wright LL, Zhou HQ Bioorg Med Chem Lett. 2005 Aug 1;15(15):3540-6. PMID:15982880<ref>PMID:15982880</ref>
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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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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1yt7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YT7 OCA].
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</div>
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<div class="pdbe-citations 1yt7" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Cathepsin|Cathepsin]]
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*[[Cathepsin 3D structures|Cathepsin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015982880</ref><references group="xtra"/><references/>
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__TOC__
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[[Category: Cathepsin K]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Barrett, D G.]]
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[[Category: Large Structures]]
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[[Category: Boncek, V M.]]
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[[Category: Barrett DG]]
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[[Category: Catalano, J G.]]
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[[Category: Boncek VM]]
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[[Category: Deaton, D N.]]
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[[Category: Catalano JG]]
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[[Category: Hassell, A M.]]
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[[Category: Deaton DN]]
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[[Category: Jurgensen, C H.]]
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[[Category: Hassell AM]]
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[[Category: Long, S T.]]
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[[Category: Jurgensen CH]]
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[[Category: McFadyen, R B.]]
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[[Category: Long ST]]
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[[Category: Miller, A B.]]
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[[Category: McFadyen RB]]
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[[Category: Miller, L R.]]
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[[Category: Miller AB]]
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[[Category: Payne, J A.]]
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[[Category: Miller LR]]
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[[Category: Ray, J A.]]
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[[Category: Payne JA]]
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[[Category: Samano, V.]]
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[[Category: Ray JA]]
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[[Category: Shewchuk, L M.]]
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[[Category: Samano V]]
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[[Category: Tavares, F X.]]
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[[Category: Shewchuk LM]]
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[[Category: Wells-Knecht, K J.]]
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[[Category: Tavares FX]]
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[[Category: Willard, D H.]]
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[[Category: Wells-Knecht KJ]]
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[[Category: Wright, L L.]]
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[[Category: Willard DH]]
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[[Category: Zhou, H Q.]]
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[[Category: Wright LL]]
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[[Category: Cathepsin]]
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[[Category: Zhou HQ]]
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[[Category: Cysteine protease]]
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[[Category: Hydrolase]]
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Current revision

Cathepsin K complexed with a constrained ketoamide inhibitor

PDB ID 1yt7

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