5ja7: Difference between revisions
m Protected "5ja7" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
==Human cathepsin K mutant C25S in complex with the allosteric effector NSC94914== | |||
<StructureSection load='5ja7' size='340' side='right' caption='[[5ja7]], [[Resolution|resolution]] 1.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ja7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JA7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JA7 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6HM:[([1,1-BIPHENYL]-2-YL)METHYL]PROPANEDIOIC+ACID'>6HM</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5ja7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ja7 OCA], [http://pdbe.org/5ja7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ja7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ja7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ja7 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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5ja7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cathepsin K]] | |||
[[Category: Korenc, M]] | |||
[[Category: Lenarcic, B]] | |||
[[Category: Novinec, M]] | [[Category: Novinec, M]] | ||
[[Category: | [[Category: Allostery cysteine peptidase proteolysis enzyme regulation collagenase]] | ||
[[Category: | [[Category: Hydrolase]] | ||