2r6n: Difference between revisions

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[[Image:2r6n.jpg|left|200px]]


{{Structure
==Crystal structure of a pyrrolopyrimidine inhibitor in complex with human Cathepsin K==
|PDB= 2r6n |SIZE=350|CAPTION= <scene name='initialview01'>2r6n</scene>, resolution 1.950&Aring;
<StructureSection load='2r6n' size='340' side='right'caption='[[2r6n]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CKE:1-{7-CYCLOHEXYL-6-[4-(4-METHYLPIPERAZIN-1-YL)BENZYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-2-YL}METHANAMINE'>CKE</scene>
<table><tr><td colspan='2'>[[2r6n]] 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=2R6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R6N FirstGlance]. <br>
|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
|GENE= CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CKE:1-{7-CYCLOHEXYL-6-[4-(4-METHYLPIPERAZIN-1-YL)BENZYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-2-YL}METHANAMINE'>CKE</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2r6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r6n OCA], [https://pdbe.org/2r6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r6n RCSB], [https://www.ebi.ac.uk/pdbsum/2r6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r6n ProSAT]</span></td></tr>
|RELATEDENTRY=[[1u9v|1U9V]], [[1u9w|1U9W]], [[1u9x|1U9X]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r6n OCA], [http://www.ebi.ac.uk/pdbsum/2r6n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2r6n RCSB]</span>
== 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/r6/2r6n_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=2r6n ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pyrrolopyrimidine, a novel scaffold, allows to adjust interactions within the S3 subsite of cathepsin K. The core intermediate 10 facilitated the P3 optimization and identified highly potent and selective cathepsin K inhibitors 11-20.


'''Crystal structure of a pyrrolopyrimidine inhibitor in complex with human Cathepsin K'''
Novel scaffold for cathepsin K inhibitors.,Teno N, Miyake T, Ehara T, Irie O, Sakaki J, Ohmori O, Gunji H, Matsuura N, Masuya K, Hitomi Y, Nonomura K, Horiuchi M, Gohda K, Iwasaki A, Umemura I, Tada S, Kometani M, Iwasaki G, Cowan-Jacob SW, Missbach M, Lattmann R, Betschart C Bioorg Med Chem Lett. 2007 Nov 15;17(22):6096-100. Epub 2007 Sep 15. PMID:17911019<ref>PMID:17911019</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2r6n" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
Pyrrolopyrimidine, a novel scaffold, allows to adjust interactions within the S3 subsite of cathepsin K. The core intermediate 10 facilitated the P3 optimization and identified highly potent and selective cathepsin K inhibitors 11-20.
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
 
== References ==
==About this Structure==
<references/>
2R6N is a [[Single protein]] structure of 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=2R6N OCA].
__TOC__
 
</StructureSection>
==Reference==
Novel scaffold for cathepsin K inhibitors., Teno N, Miyake T, Ehara T, Irie O, Sakaki J, Ohmori O, Gunji H, Matsuura N, Masuya K, Hitomi Y, Nonomura K, Horiuchi M, Gohda K, Iwasaki A, Umemura I, Tada S, Kometani M, Iwasaki G, Cowan-Jacob SW, Missbach M, Lattmann R, Betschart C, Bioorg Med Chem Lett. 2007 Nov 15;17(22):6096-100. Epub 2007 Sep 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17911019 17911019]
[[Category: Cathepsin K]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Cowan-Jacob, S W.]]
[[Category: Cowan-Jacob SW]]
[[Category: Geisse, S.]]
[[Category: Geisse S]]
[[Category: Mathis, B.]]
[[Category: Mathis B]]
[[Category: Ramage, P.]]
[[Category: Ramage P]]
[[Category: covalent bond to inhibitor]]
[[Category: disease mutation]]
[[Category: glycoprotein]]
[[Category: hydrolase]]
[[Category: lysosome]]
[[Category: protease]]
[[Category: thiol protease]]
[[Category: zymogen]]
 
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