3h7d: Difference between revisions

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-{{Seed}}
-[[Image:3h7d.jpg|left|200px]]
-<!--
+==The crystal structure of the cathepsin K Variant M5 in complex with chondroitin-4-sulfate==
-The line below this paragraph, containing "STRUCTURE_3h7d", creates the "Structure Box" on the page.
+<StructureSection load='3h7d' size='340' side='right'caption='[[3h7d]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3h7d]] is a 2 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=3H7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H7D FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.242&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASG:2-DEOXY-2-ACETAMIDO-BETA-D-GALACTOSE-4-SULFATE'>ASG</scene>, <scene name='pdbligand=BDP:BETA-D-GLUCOPYRANURONIC+ACID'>BDP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=E64:N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE'>E64</scene></td></tr>
-{{STRUCTURE_3h7d|  PDB=3h7d  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3h7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h7d OCA], [https://pdbe.org/3h7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h7d RCSB], [https://www.ebi.ac.uk/pdbsum/3h7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h7d 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/h7/3h7d_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=3h7d ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In the presence of oligomeric chondroitin 4-sulfate (C4-S), cathepsin K (catK) forms a specific complex that was shown to be the source of the major collagenolytic activity in bone osteoclasts. C4-S forms multiple contacts with amino acid residues on the backside of the catK molecule that help to facilitate complex formation. As cathepsin L does not exhibit a significant collagenase activity in the presence or in the absence of C4-S, we substituted the C4-S interacting residues in catK with those of cathepsin L. Variants revealed altered collagenolytic activities with the largest inhibitory effect shown by the hexavariant M5. None of the variants showed a reduction in their gelatinolytic and peptidolytic activities when compared with wild-type catK, indicating no structural alteration within their active sites. However, the crystal structure of the M5 variant in the presence of oligomeric C4-S revealed a different binding of chondroitin 4-sulfate. C4-S is not continuously ordered as it is in the wild-type catK.C4-S complex. The orientation and the direction of the hexasaccharide on the catK surface have changed, so that the hexasaccharide is positioned between two symmetry-related molecules. Only one M5 variant molecule of the dimer that is present in the asymmetric unit interacts with C4-S. These substitutions have changed the mode of catK binding to C4-S and, as a result, have likely affected the collagenolytic potential of the variant. The data presented here support our hypothesis that distinct catK/C4-S interactions are necessary for the collagenolytic activity of the enzyme.
-===The crystal structure of the cathepsin K Variant M5 in complex with chondroitin-4-sulfate===
+Structure-activity analysis of cathepsin K/chondroitin 4-sulfate interactions.,Cherney MM, Lecaille F, Kienitz M, Nallaseth FS, Li Z, James MN, Bromme D J Biol Chem. 2011 Mar 18;286(11):8988-98. Epub 2010 Dec 30. PMID:21193413<ref>PMID:21193413</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3h7d" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-H7D is a 2 chains structure with sequences 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=3H7D OCA].
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-[[Category: Cathepsin K]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bromme, D.]]
+[[Category: Large Structures]]
-[[Category: Cherney, M M.]]
+[[Category: Bromme D]]
-[[Category: James, M N.G.]]
+[[Category: Cherney MM]]
-[[Category: Kienetz, M.]]
+[[Category: James MNG]]
-[[Category: Cathepsin k mutant]]
+[[Category: Kienetz M]]
-[[Category: Disease mutation]]
-[[Category: Disulfide bond]]
-[[Category: Glycoprotein]]
-[[Category: Glycosaminoglycan]]
-[[Category: Hydrolase]]
-[[Category: Lysosome]]
-[[Category: Protease]]
-[[Category: Sulfhydryl peptidase]]
-[[Category: Ternary complex]]
-[[Category: Thiol protease]]
-[[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 28 11:03:48 2010''