3ljt: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image: | ==Crystal Structure of the Catalytic Domain of ADAMTS-5 in Complex with an Amino-2-indanol compound== | ||
<StructureSection load='3ljt' size='340' side='right' caption='[[3ljt]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ljt]] is a 1 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=3LJT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LJT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LA3:(2R)-2-[4-(1,3-BENZODIOXOL-5-YL)BENZYL]-N~4~-HYDROXY-N~1~-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]BUTANEDIAMIDE'>LA3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hy9|3hy9]], [[3hyg|3hyg]], [[3ljz|3ljz]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAMTS-5, ADAMTS11, ADAMTS5, ADMP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3ljt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ljt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ljt RCSB], [http://www.ebi.ac.uk/pdbsum/3ljt PDBsum]</span></td></tr> | |||
</table> | |||
== 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/lj/3ljt_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A ((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl) succinamide derivative (here referred to as Compound 12) shows significant activity toward many matrix metalloproteinases (MMPs), including MMP-2, MMP-8, MMP-9, and MMP-13. Modeling studies had predicted that this compound would not bind to ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) due to its shallow S1' pocket. However, inhibition analysis revealed it to be a nanomolar inhibitor of both ADAMTS-4 and -5. The observed inconsistency was explained by analysis of crystallographic structures, which showed that Compound 12 in complex with the catalytic domain of ADAMTS-5 (cataTS5) exhibits an unusual conformation in the S1' pocket of the protein. This first demonstration that cataTS5 can undergo an induced conformational change in its active site pocket by a molecule like Compound 12 should enable the design of new aggrecanase inhibitors with better potency and selectivity profiles. | |||
Structure analysis reveals the flexibility of the ADAMTS-5 active site.,Shieh HS, Tomasselli AG, Mathis KJ, Schnute ME, Woodard SS, Caspers N, Williams JM, Kiefer JR, Munie G, Wittwer A, Malfait AM, Tortorella MD Protein Sci. 2011 Apr;20(4):735-44. doi: 10.1002/pro.606. PMID:21370305<ref>PMID:21370305</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]] | *[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]] | ||
*[[Superoxide Dismutase|Superoxide Dismutase]] | *[[Superoxide Dismutase|Superoxide Dismutase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Caspers, N | [[Category: Caspers, N]] | ||
[[Category: Shieh, H S | [[Category: Shieh, H S]] | ||
[[Category: Williams, J M | [[Category: Williams, J M]] | ||
[[Category: Alpha/beta structure]] | [[Category: Alpha/beta structure]] | ||
[[Category: Central five stranded beta-sheet]] | [[Category: Central five stranded beta-sheet]] | ||
Revision as of 08:48, 9 December 2014
Crystal Structure of the Catalytic Domain of ADAMTS-5 in Complex with an Amino-2-indanol compound
| ||||||||||||
