1yk8: Difference between revisions

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<StructureSection load='1yk8' size='340' side='right'caption='[[1yk8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='1yk8' size='340' side='right'caption='[[1yk8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1yk8]] is a 1 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=1YK8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1YK8 FirstGlance]. <br>
<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>
</td></tr><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>
</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>
<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='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>
<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'>[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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1yk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yk8 OCA], [http://pdbe.org/1yk8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yk8 RCSB], [http://www.ebi.ac.uk/pdbsum/1yk8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yk8 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== 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>
[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 ==
== 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.  
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cathepsin K]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Barrett, D G]]
[[Category: Barrett DG]]
[[Category: Deaton, D N]]
[[Category: Deaton DN]]
[[Category: Hassell, A M]]
[[Category: Hassell AM]]
[[Category: McFadyen, R B]]
[[Category: McFadyen RB]]
[[Category: Miller, A B]]
[[Category: Miller AB]]
[[Category: Miller, L R]]
[[Category: Miller LR]]
[[Category: Payne, J A]]
[[Category: Payne JA]]
[[Category: Shewchuk, L M]]
[[Category: Shewchuk LM]]
[[Category: Willard, D H]]
[[Category: Willard DH]]
[[Category: Wright, L L]]
[[Category: Wright LL]]
[[Category: Cathepsin]]
[[Category: Catk]]
[[Category: Cysteine]]
[[Category: Hydrolase]]
[[Category: Protease]]

Revision as of 09:57, 23 August 2023

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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