5jh3

From Proteopedia

(Difference between revisions)

Revision as of 18:35, 10 December 2016

Human cathepsin K mutant C25S

Structural highlights

5jh3 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	Cathepsin K, with EC number 3.4.22.38
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.

Publication Abstract from PubMed

The cysteine peptidase cathepsin K is a potent collagenolytic enzyme and a promising target for the treatment of osteoporosis. Here, we characterize its allosteric fine-tuning via a recently identified allosteric site. We show that compound NSC94914 binds this site and acts as a specific partial inhibitor of the collagenolytic activity of cathepsin K. We link the functional differences between NSC94914 and known effectors (compound NSC11345 and glycosaminoglycans) to their different modes of interaction with the site. We characterize the allosteric site by site-directed mutagenesis and show that it is involved in specific regulation of the collagenolytic activity of cathepsin K.

An allosteric site enables fine-tuning of cathepsin K by diverse effectors.,Novinec M, Rebernik M, Lenarcic B FEBS Lett. 2016 Nov 17. doi: 10.1002/1873-3468.12495. PMID:27859061^[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
↑ Novinec M, Rebernik M, Lenarcic B. An allosteric site enables fine-tuning of cathepsin K by diverse effectors. FEBS Lett. 2016 Nov 17. doi: 10.1002/1873-3468.12495. PMID:27859061 doi:http://dx.doi.org/10.1002/1873-3468.12495

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jh3"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5jh3 is ON HOLD  until Paper Publication
+==Human cathepsin K mutant C25S==
+<StructureSection load='5jh3' size='340' side='right' caption='[[5jh3]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5jh3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JH3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JH3 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jh3 OCA], [http://pdbe.org/5jh3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jh3 RCSB], [http://www.ebi.ac.uk/pdbsum/5jh3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jh3 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>
+== 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The cysteine peptidase cathepsin K is a potent collagenolytic enzyme and a promising target for the treatment of osteoporosis. Here, we characterize its allosteric fine-tuning via a recently identified allosteric site. We show that compound NSC94914 binds this site and acts as a specific partial inhibitor of the collagenolytic activity of cathepsin K. We link the functional differences between NSC94914 and known effectors (compound NSC11345 and glycosaminoglycans) to their different modes of interaction with the site. We characterize the allosteric site by site-directed mutagenesis and show that it is involved in specific regulation of the collagenolytic activity of cathepsin K.
-Authors: Novinec, M., Korenc, M., Lenarcic, B.
+An allosteric site enables fine-tuning of cathepsin K by diverse effectors.,Novinec M, Rebernik M, Lenarcic B FEBS Lett. 2016 Nov 17. doi: 10.1002/1873-3468.12495. PMID:27859061<ref>PMID:27859061</ref>
-Description: Human cathepsin K mutant C25S
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Novinec, M]]
+<div class="pdbe-citations 5jh3" style="background-color:#fffaf0;"></div>
-[[Category: Lenarcic, B]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Cathepsin K]]
 [[Category: Korenc, M]]
+[[Category: Lenarcic, B]]
+[[Category: Novinec, M]]
+[[Category: Allostery cysteine]]
+[[Category: Collagenase]]
+[[Category: Enzyme regulation]]
+[[Category: Hydrolase]]
+[[Category: Peptidase proteolysis]]

5jh3

From Proteopedia

Revision as of 18:35, 10 December 2016

Human cathepsin K mutant C25S

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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