3o0u

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Revision as of 10:02, 14 February 2024

Cathepsin K covalently bound to a cyano-pyrimidine inhibitor with improved selectivity over hERG

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OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o0u"

Categories: Homo sapiens | Large Structures | Fradera X | Uitdehaag JCM | Van Zeeland M

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 <StructureSection load='3o0u' size='340' side='right'caption='[[3o0u]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o0u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O0U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o0u]] 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=3O0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O0U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O47:3-{2-[(E)-IMINOMETHYL]-6-PROPYLPYRIMIDIN-4-YL}-N,N-DIMETHYL-5-(TRIFLUOROMETHYL)BENZAMIDE'>O47</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]] 1.8&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSK, CTSO, CTSO2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O47:3-{2-[(E)-IMINOMETHYL]-6-PROPYLPYRIMIDIN-4-YL}-N,N-DIMETHYL-5-(TRIFLUOROMETHYL)BENZAMIDE'>O47</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [https://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=3o0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o0u OCA], [https://pdbe.org/3o0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o0u RCSB], [https://www.ebi.ac.uk/pdbsum/3o0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o0u 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>
+[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.
+[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.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of clogP and pK(a) properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (&gt;1000-fold), displayed a highly attractive overall profile.
-Optimisation of 2-cyano-pyrimidine inhibitors of cathepsin K: Improving selectivity over hERG.,Rankovic Z, Cai J, Kerr J, Fradera X, Robinson J, Mistry A, Finlay W, McGarry G, Andrews F, Caulfield W, Cumming I, Dempster M, Waller J, Arbuckle W, Anderson M, Martin I, Mitchell A, Long C, Baugh M, Westwood P, Kinghorn E, Jones P, Uitdehaag JC, van Zeeland M, Potin D, Saniere L, Fouquet A, Chevallier F, Deronzier H, Dorleans C, Nicolai E Bioorg Med Chem Lett. 2010 Aug 24. PMID:20843687<ref>PMID:20843687</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3o0u" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 29: / Line 19: @@
 __TOC__
 </StructureSection>
-[[Category: Cathepsin K]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[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: Bone]]
-[[Category: Covalent 2-cyano-pyrimidine inhibitor]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Reversible covalent bond between cys25 and ligand]]

3o0u

From Proteopedia

Revision as of 10:02, 14 February 2024

Cathepsin K covalently bound to a cyano-pyrimidine inhibitor with improved selectivity over hERG

Structural highlights

Disease

Function

See Also

References

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