1yk7: Difference between revisions

Revision as of 06:57, 23 August 2023

Cathepsin K complexed with a cyanopyrrolidine inhibitor

Structural highlights

1yk7 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 2.5Å
Ligands:	NBL
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 a PDE IV inhibitor hit derived from high throughput screening of the compound collection, a key pyrrolidine cyanamide pharmacophore was identified. Modifications of the pyrrolidine ring produced enhancements in cathepsin K inhibition. An X-ray co-crystal structure of a cyanamide with cathepsin K confirmed the mode of inhibition.

Novel and potent cyclic cyanamide-based cathepsin K inhibitors.,Deaton DN, Hassell AM, McFadyen RB, Miller AB, Miller LR, Shewchuk LM, Tavares FX, Willard DH Jr, Wright LL Bioorg Med Chem Lett. 2005 Apr 1;15(7):1815-9. PMID:15780613^[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
↑ Deaton DN, Hassell AM, McFadyen RB, Miller AB, Miller LR, Shewchuk LM, Tavares FX, Willard DH Jr, Wright LL. Novel and potent cyclic cyanamide-based cathepsin K inhibitors. Bioorg Med Chem Lett. 2005 Apr 1;15(7):1815-9. PMID:15780613 doi:https://dx.doi.org/10.1016/j.bmcl.2005.02.033

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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] Deaton DN, Hassell AM, McFadyen RB, Miller AB, Miller LR, Shewchuk LM, Tavares FX, Willard DH Jr, Wright LL. Novel and potent cyclic cyanamide-based cathepsin K inhibitors. Bioorg Med Chem Lett. 2005 Apr 1;15(7):1815-9. PMID:15780613 doi:https://dx.doi.org/10.1016/j.bmcl.2005.02.033

[1]

[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 <StructureSection load='1yk7' size='340' side='right'caption='[[1yk7]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1yk7]] 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=1YK7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1YK7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1yk7]] 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=1YK7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YK7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NBL:N2-[(BENZYLOXY)CARBONYL]-N1-[(3S)-1-CYANOPYRROLIDIN-3-YL]-L-LEUCINAMIDE'>NBL</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]] 2.5&#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=NBL:N2-[(BENZYLOXY)CARBONYL]-N1-[(3S)-1-CYANOPYRROLIDIN-3-YL]-L-LEUCINAMIDE'>NBL</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=1yk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yk7 OCA], [https://pdbe.org/1yk7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yk7 RCSB], [https://www.ebi.ac.uk/pdbsum/1yk7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yk7 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=1yk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yk7 OCA], [http://pdbe.org/1yk7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yk7 RCSB], [http://www.ebi.ac.uk/pdbsum/1yk7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yk7 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>
+[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 ==
-[[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 39: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Cathepsin K]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[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: Shewchuk, L M]]
+[[Category: Shewchuk LM]]
-[[Category: Tavares, F X]]
+[[Category: Tavares FX]]
-[[Category: Willard, D H]]
+[[Category: Willard DH]]
-[[Category: Wright, L L]]
+[[Category: Wright LL]]
-[[Category: Cathepsin]]
-[[Category: Catk]]
-[[Category: Cysteine]]
-[[Category: Hydrolase]]
-[[Category: Protease]]

1yk7: Difference between revisions

Revision as of 06:57, 23 August 2023

Cathepsin K complexed with a cyanopyrrolidine inhibitor

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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