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[[Image:3b2z.jpg|left|200px]]
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{{STRUCTURE_3b2z|  PDB=3b2z  |  SCENE=  }}
'''Crystal Structure of ADAMTS4 (apo form)'''


==Crystal Structure of ADAMTS4 (apo form)==
<StructureSection load='3b2z' size='340' side='right'caption='[[3b2z]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3b2z]] is a 8 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=3B2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B2Z 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3b2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b2z OCA], [https://pdbe.org/3b2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b2z RCSB], [https://www.ebi.ac.uk/pdbsum/3b2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b2z ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATS4_HUMAN ATS4_HUMAN] Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site.
== 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/b2/3b2z_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=3b2z ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor-bound enzymes exhibit two essentially different catalytic-site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.


==Overview==
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.,Mosyak L, Georgiadis K, Shane T, Svenson K, Hebert T, McDonagh T, Mackie S, Olland S, Lin L, Zhong X, Kriz R, Reifenberg EL, Collins-Racie LA, Corcoran C, Freeman B, Zollner R, Marvell T, Vera M, Sum PE, Lavallie ER, Stahl M, Somers W Protein Sci. 2008 Jan;17(1):16-21. Epub 2007 Nov 27. PMID:18042673<ref>PMID:18042673</ref>
Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor-bound enzymes exhibit two essentially different catalytic-site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
3B2Z 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=3B2Z OCA].
</div>
<div class="pdbe-citations 3b2z" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5., Mosyak L, Georgiadis K, Shane T, Svenson K, Hebert T, McDonagh T, Mackie S, Olland S, Lin L, Zhong X, Kriz R, Reifenberg EL, Collins-Racie LA, Corcoran C, Freeman B, Zollner R, Marvell T, Vera M, Sum PE, Lavallie ER, Stahl M, Somers W, Protein Sci. 2008 Jan;17(1):16-21. Epub 2007 Nov 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18042673 18042673]
*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
[[Category: ADAMTS-4 endopeptidase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Mosyak, L.]]
[[Category: Mosyak L]]
[[Category: Somers, W.]]
[[Category: Somers W]]
[[Category: Stahl, M.]]
[[Category: Stahl M]]
[[Category: Aggrecanase]]
[[Category: Cleavage on pair of basic residue]]
[[Category: Extracellular matrix]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Metal-binding]]
[[Category: Metalloprotease]]
[[Category: Polymorphism]]
[[Category: Secreted]]
[[Category: Zinc]]
[[Category: Zymogen]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 20:20:40 2008''

Latest revision as of 09:42, 6 November 2024

Crystal Structure of ADAMTS4 (apo form)

3b2z, resolution 2.80Å

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