2a8h: Difference between revisions

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-[[Image:2a8h.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2a8h", creates the "Structure Box" on the page.
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-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_2a8h|  PDB=2a8h  |  SCENE=  }}
-'''Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor'''
+==Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor==
+<StructureSection load='2a8h' size='340' side='right'caption='[[2a8h]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2a8h]] 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=2A8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A8H 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4NH:4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE'>4NH</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=2a8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a8h OCA], [https://pdbe.org/2a8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a8h RCSB], [https://www.ebi.ac.uk/pdbsum/2a8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a8h ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:[https://omim.org/entry/614328 614328]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.<ref>PMID:22010916</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN] Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity).<ref>PMID:12441351</ref> <ref>PMID:20592283</ref>
+== 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/a8/2a8h_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=2a8h ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.
-==Overview==
+Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.,Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D, Skotnicki JS Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19. PMID:16426848<ref>PMID:16426848</ref>
-A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-A8H 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=2A8H OCA].
+</div>
+<div class="pdbe-citations 2a8h" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates., Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D, Skotnicki JS, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16426848 16426848]
+*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
-[[Category: ADAM 17 endopeptidase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Barone, D.]]
+[[Category: Barone D]]
-[[Category: Chen, J M.]]
+[[Category: Chen JM]]
-[[Category: Cummons, T.]]
+[[Category: Cummons T]]
-[[Category: Du, M.]]
+[[Category: Du M]]
-[[Category: Jin, G.]]
+[[Category: Jin G]]
-[[Category: Laakso, L M.]]
+[[Category: Laakso LM]]
-[[Category: Levin, J I.]]
+[[Category: Levin JI]]
-[[Category: Schmid, J.]]
+[[Category: Schmid J]]
-[[Category: Skotnicki, J S.]]
+[[Category: Skotnicki JS]]
-[[Category: Xu, J.]]
+[[Category: Xu J]]
-[[Category: Xu, W.]]
+[[Category: Xu W]]
-[[Category: Tace-inhibitor complex]]
-[[Category: Tace/adam-17]]
-[[Category: Zn-endopeptidase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:44:38 2008''