View source for 3hyg


==Crystal Structure of the Catalytic Domain of ADAMTS-5 in Complex with an Amino-2-indanol compound==
<StructureSection load='3hyg' size='340' side='right'caption='[[3hyg]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3hyg]] 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=3HYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HYG 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]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=099:(2R)-N~4~-HYDROXY-2-(3-HYDROXYBENZYL)-N~1~-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]BUTANEDIAMIDE'>099</scene>, <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=3hyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hyg OCA], [https://pdbe.org/3hyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hyg RCSB], [https://www.ebi.ac.uk/pdbsum/3hyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hyg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATS5_HUMAN ATS5_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. May play a role in proteolytic processing mostly during the peri-implantation period.
== 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/hy/3hyg_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=3hyg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several inhibitors of a series of cis-1(S)2(R)-amino-2-indanol-based compounds were reported to be selective for the aggrecanases, ADAMTS-4 and -5 over other metalloproteases. To understand the nature of this selectivity for aggrecanases, the inhibitors, along with the broad spectrum metalloprotease inhibitor marimastat, were independently bound to the catalytic domain of ADAMTS-5, and the corresponding crystal structures were determined. By comparing the structures, it was determined that the specificity of the relative inhibitors for ADAMTS-5 was not driven by a specific interaction, such as zinc chelation, hydrogen bonding, or charge interactions, but rather by subtle and indirect factors, such as water bridging, ring rigidity, pocket size, and shape, as well as protein conformation flexibility.

Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors.,Tortorella MD, Tomasselli AG, Mathis KJ, Schnute ME, Woodard SS, Munie G, Williams JM, Caspers N, Wittwer AJ, Malfait AM, Shieh HS J Biol Chem. 2009 Sep 4;284(36):24185-91. Epub 2009 Jul 8. PMID:19586907<ref>PMID:19586907</ref>

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

==See Also==
*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Caspers N]]
[[Category: Mathis KJ]]
[[Category: Shieh H-S]]
[[Category: Tomasselli A]]
[[Category: Tortorella MD]]
[[Category: Williams JM]]