This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3kwb

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:17, 2 January 2019) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3kwb.png|left|200px]]
 
-
{{STRUCTURE_3kwb| PDB=3kwb | SCENE= }}
+
==Structure of CatK covalently bound to a dioxo-triazine inhibitor==
 +
<StructureSection load='3kwb' size='340' side='right' caption='[[3kwb]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3kwb]] is a 2 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=3KWB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KWB FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ORH:3,5-DIOXO-4-(3-PIPERIDIN-1-YLPROPYL)-2-[3-(TRIFLUOROMETHYL)PHENYL]-2,3,4,5-TETRAHYDRO-1,2,4-TRIAZINE-6-CARBONITRILE'>ORH</scene></td></tr>
 +
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kw9|3kw9]]</td></tr>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwb OCA], [http://pdbe.org/3kwb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kwb RCSB], [http://www.ebi.ac.uk/pdbsum/3kwb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kwb ProSAT]</span></td></tr>
 +
</table>
 +
== 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>
 +
== 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.
 +
== 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/3kwb_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3kwb ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC(50) values of 17nM against catK and &gt;10,000nM in catL, catB and catS assays.
-
===Structure of CatK covalently bound to a dioxo-triazine inhibitor===
+
Dioxo-triazines as a novel series of cathepsin K inhibitors.,Rankovic Z, Cai J, Fradera X, Dempster M, Mistry A, Mitchell A, Long C, Hamilton E, King A, Boucharens S, Jamieson C, Gillespie J, Cumming I, Uitdehaag J, van Zeeland M Bioorg Med Chem Lett. 2010 Mar 1;20(5):1488-90. Epub 2010 Jan 25. PMID:20153187<ref>PMID:20153187</ref>
-
{{ABSTRACT_PUBMED_20153187}}
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
==About this Structure==
+
<div class="pdbe-citations 3kwb" style="background-color:#fffaf0;"></div>
-
[[3kwb]] is a 2 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=3KWB OCA].
+
==See Also==
==See Also==
*[[Cathepsin|Cathepsin]]
*[[Cathepsin|Cathepsin]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:020153187</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
[[Category: Cathepsin K]]
[[Category: Cathepsin K]]
-
[[Category: Homo sapiens]]
+
[[Category: Human]]
-
[[Category: Uitdehaag, J C.M.]]
+
[[Category: Uitdehaag, J C.M]]
-
[[Category: Zeeland, M van.]]
+
[[Category: Zeeland, M van]]
[[Category: Covalent bond]]
[[Category: Covalent bond]]
[[Category: Cys 25]]
[[Category: Cys 25]]

Current revision

Structure of CatK covalently bound to a dioxo-triazine inhibitor

3kwb, resolution 2.02Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3kwb"
Personal tools