1yk8: Difference between revisions

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[[Image:1yk8.png|left|200px]]


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==Cathepsin K complexed with a cyanamide-based inhibitor==
The line below this paragraph, containing "STRUCTURE_1yk8", creates the "Structure Box" on the page.
<StructureSection load='1yk8' size='340' side='right'caption='[[1yk8]], [[Resolution|resolution]] 2.60&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'>[[1yk8]] 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=1YK8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YK8 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]] 2.6&#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=T2M:TERT-BUTYL+2-CYANO-2-METHYLHYDRAZINECARBOXYLATE'>T2M</scene></td></tr>
{{STRUCTURE_1yk8|  PDB=1yk8  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yk8 OCA], [https://pdbe.org/1yk8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yk8 RCSB], [https://www.ebi.ac.uk/pdbsum/1yk8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yk8 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/yk/1yk8_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=1yk8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Conversion of the proline-derived cyanamide lead to an acyclic cyanamide capable of forming an additional hydrogen bond with cathepsin K resulted in a large increase in inhibitory activity. An X-ray structure of a co-crystal of a cyanamide with cathepsin K confirmed the enzyme interaction. Furthermore, a representative acyclic cyanamide inhibitor 6r was able to attenuate bone resorption in the rat calvarial model.


===Cathepsin K complexed with a cyanamide-based inhibitor===
Acyclic cyanamide-based inhibitors of cathepsin K.,Barrett DG, Deaton DN, Hassell AM, McFadyen RB, Miller AB, Miller LR, Payne JA, Shewchuk LM, Willard DH Jr, Wright LL Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43. PMID:15896958<ref>PMID:15896958</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1yk8" style="background-color:#fffaf0;"></div>
(as it appears on PubMed at http://www.pubmed.gov), where 15896958 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15896958}}
 
==About this Structure==
[[1yk8]] is a 1 chain structure of [[Cathepsin]] 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=1YK8 OCA].


==See Also==
==See Also==
*[[Cathepsin]]
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:15896958</ref><references group="xtra"/>
__TOC__
[[Category: Cathepsin K]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Barrett, D G.]]
[[Category: Large Structures]]
[[Category: Deaton, D N.]]
[[Category: Barrett DG]]
[[Category: Hassell, A M.]]
[[Category: Deaton DN]]
[[Category: McFadyen, R B.]]
[[Category: Hassell AM]]
[[Category: Miller, A B.]]
[[Category: McFadyen RB]]
[[Category: Miller, L R.]]
[[Category: Miller AB]]
[[Category: Payne, J A.]]
[[Category: Miller LR]]
[[Category: Shewchuk, L M.]]
[[Category: Payne JA]]
[[Category: Willard, D H.]]
[[Category: Shewchuk LM]]
[[Category: Wright, L L.]]
[[Category: Willard DH]]
[[Category: Cathepsin]]
[[Category: Wright LL]]
[[Category: Catk]]
[[Category: Cysteine]]
[[Category: Hydrolase]]
[[Category: Protease]]

Latest revision as of 11:57, 6 November 2024

Cathepsin K complexed with a cyanamide-based inhibitorCathepsin K complexed with a cyanamide-based inhibitor

Structural highlights

1yk8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CATK_HUMAN Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.[1] [2] [3] [4]

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Conversion of the proline-derived cyanamide lead to an acyclic cyanamide capable of forming an additional hydrogen bond with cathepsin K resulted in a large increase in inhibitory activity. An X-ray structure of a co-crystal of a cyanamide with cathepsin K confirmed the enzyme interaction. Furthermore, a representative acyclic cyanamide inhibitor 6r was able to attenuate bone resorption in the rat calvarial model.

Acyclic cyanamide-based inhibitors of cathepsin K.,Barrett DG, Deaton DN, Hassell AM, McFadyen RB, Miller AB, Miller LR, Payne JA, Shewchuk LM, Willard DH Jr, Wright LL Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43. PMID:15896958[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996 Aug 30;273(5279):1236-8. PMID:8703060
  2. ↑ Gelb BD, Willner JP, Dunn TM, Kardon NB, Verloes A, Poncin J, Desnick RJ. Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis. Am J Hum Genet. 1998 Apr;62(4):848-54. PMID:9529353 doi:S0002-9297(07)60977-X
  3. ↑ Ho N, Punturieri A, Wilkin D, Szabo J, Johnson M, Whaley J, Davis J, Clark A, Weiss S, Francomano C. Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein. J Bone Miner Res. 1999 Oct;14(10):1649-53. PMID:10491211
  4. ↑ Haagerup A, Hertz JM, Christensen MF, Binderup H, Kruse TA. Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population. Eur J Hum Genet. 2000 Jun;8(6):431-6. PMID:10878663 doi:10.1038/sj.ejhg.5200481
  5. ↑ Barrett DG, Deaton DN, Hassell AM, McFadyen RB, Miller AB, Miller LR, Payne JA, Shewchuk LM, Willard DH Jr, Wright LL. Acyclic cyanamide-based inhibitors of cathepsin K. Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43. PMID:15896958 doi:10.1016/j.bmcl.2005.04.032

1yk8, resolution 2.60Å

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