1u9w: Difference between revisions

Latest revision as of 07:31, 30 October 2024

Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABI491

Structural highlights

1u9w 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 2.3Å
Ligands:	IHI
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

Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.

Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K.,Altmann E, Cowan-Jacob SW, Missbach M J Med Chem. 2004 Nov 18;47(24):5833-6. PMID:15537340^[5]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ Altmann E, Cowan-Jacob SW, Missbach M. Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K. J Med Chem. 2004 Nov 18;47(24):5833-6. PMID:15537340 doi:10.1021/jm0493111

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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] Altmann E, Cowan-Jacob SW, Missbach M. Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K. J Med Chem. 2004 Nov 18;47(24):5833-6. PMID:15537340 doi:10.1021/jm0493111

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[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-[[Image:1u9w.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1u9w", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_1u9w|  PDB=1u9w  |  SCENE=  }}
-'''Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABI491'''
+==Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABI491==
+<StructureSection load='1u9w' size='340' side='right'caption='[[1u9w]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1u9w]] 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=1U9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U9W FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHI:9-CYCLOPENTYL-6-[2-(3-IMIDAZOL-1-YL-PROPOXY)-PHENYLAMINO]-9H-PURINE-2-CARBONITRILE'>IHI</scene></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=1u9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u9w OCA], [https://pdbe.org/1u9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u9w RCSB], [https://www.ebi.ac.uk/pdbsum/1u9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u9w 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/u9/1u9w_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=1u9w ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.
-==Overview==
+Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K.,Altmann E, Cowan-Jacob SW, Missbach M J Med Chem. 2004 Nov 18;47(24):5833-6. PMID:15537340<ref>PMID:15537340</ref>
-Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-U9W 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=1U9W OCA].
+</div>
+<div class="pdbe-citations 1u9w" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K., Altmann E, Cowan-Jacob SW, Missbach M, J Med Chem. 2004 Nov 18;47(24):5833-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15537340 15537340]
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-[[Category: Cathepsin K]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Cowan-Jacob, S W.]]
+[[Category: Cowan-Jacob SW]]
-[[Category: Hydrolase]]
-[[Category: Sulfhydryl proteinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 10:57:01 2008''

1u9w: Difference between revisions

Latest revision as of 07:31, 30 October 2024

Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABI491

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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