2rjp

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[[Image:2rjp.png|left|200px]]
 
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{{STRUCTURE_2rjp| PDB=2rjp | SCENE= }}
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==Crystal structure of ADAMTS4 with inhibitor bound==
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<StructureSection load='2rjp' size='340' side='right'caption='[[2rjp]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2rjp]] is a 4 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=2RJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RJP FirstGlance]. <br>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=886:N-({4-[(4-ISOBUTYRYLPHENOXY)METHYL]BIPHENYL-4-YL}SULFONYL)-D-VALINE'>886</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rjp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rjp OCA], [https://pdbe.org/2rjp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rjp RCSB], [https://www.ebi.ac.uk/pdbsum/2rjp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rjp ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rj/2rjp_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2rjp ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===Crystal structure of ADAMTS4 with inhibitor bound===
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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>
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{{ABSTRACT_PUBMED_18042673}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2rjp" style="background-color:#fffaf0;"></div>
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[[2rjp]] is a 4 chain structure with 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=2RJP OCA].
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==See Also==
==See Also==
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*[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]]
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*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018042673</ref><references group="xtra"/>
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__TOC__
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[[Category: ADAMTS-4 endopeptidase]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Mosyak, L.]]
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[[Category: Large Structures]]
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[[Category: Somers, W.]]
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[[Category: Mosyak L]]
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[[Category: Stahl, M.]]
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[[Category: Somers W]]
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[[Category: Aggrecanase]]
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[[Category: Stahl M]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Extracellular matrix]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Metal-binding]]
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[[Category: Metalloprotease domain]]
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[[Category: Secreted]]
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[[Category: Zymogen]]
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Current revision

Crystal structure of ADAMTS4 with inhibitor bound

PDB ID 2rjp

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