3o1g: Difference between revisions

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-{{Seed}}
-[[Image:3o1g.jpg|left|200px]]
-<!--
+==Cathepsin K covalently bound to a 2-cyano pyrimidine inhibitor with a benzyl P3 group.==
-The line below this paragraph, containing "STRUCTURE_3o1g", creates the "Structure Box" on the page.
+<StructureSection load='3o1g' size='340' side='right'caption='[[3o1g]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3o1g]] 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=3O1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O1G FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O75:N-BENZYL-3-(2-CYANO-6-PROPYLPYRIMIDIN-4-YL)-N-[2-(DIMETHYLAMINO)ETHYL]-5-(TRIFLUOROMETHYL)BENZAMIDE'>O75</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_3o1g|  PDB=3o1g  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3o1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o1g OCA], [https://pdbe.org/3o1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o1g RCSB], [https://www.ebi.ac.uk/pdbsum/3o1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o1g 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/o1/3o1g_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=3o1g ConSurf].
+<div style="clear:both"></div>
+<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.
-===Cathepsin K covalently bound to a 2-cyano pyrimidine inhibitor with a benzyl P3 group.===
+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 3o1g" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20843687}}, adds the Publication Abstract to the page
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20843687 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20843687}}
+__TOC__
+</StructureSection>
-==About this Structure==
-O1G 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=3O1G OCA].
-==Reference==
-<ref group="xtra">PMID:20843687</ref><references group="xtra"/>
-[[Category: Cathepsin K]]
 [[Category: Homo sapiens]]
-[[Category: Fradera, X.]]
+[[Category: Large Structures]]
-[[Category: Uitdehaag, J C.M.]]
+[[Category: Fradera X]]
-[[Category: Zeeland, M van.]]
+[[Category: Uitdehaag JCM]]
-[[Category: Bone]]
+[[Category: Van Zeeland M]]
-[[Category: Hydrolase]]
-[[Category: K protein from comp]]
-[[Category: Ligand covalently bound to cys25]]
-[[Category: Reversible covalent inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct  6 06:07:28 2010''