2a8h: Difference between revisions

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-{{Seed}}
-[[Image:2a8h.png|left|200px]]
-<!--
+==Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor==
-The line below this paragraph, containing "STRUCTURE_2a8h", creates the "Structure Box" on the page.
+<StructureSection load='2a8h' size='340' side='right'caption='[[2a8h]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</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>
-{{STRUCTURE_2a8h|  PDB=2a8h  |  SCENE=  }}
+<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.
-===Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2a8h" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16426848}}, adds the Publication Abstract to the page
+*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 16426848 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16426848}}
+__TOC__
+</StructureSection>
-==About this Structure==
-A8H is a 2 chains structure of sequences 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].
-==Reference==
-<ref group="xtra">PMID:16426848</ref><references group="xtra"/>
-[[Category: ADAM 17 endopeptidase]]
 [[Category: Homo sapiens]]
-[[Category: Barone, D.]]
+[[Category: Large Structures]]
-[[Category: Chen, J M.]]
+[[Category: Barone D]]
-[[Category: Cummons, T.]]
+[[Category: Chen JM]]
-[[Category: Du, M.]]
+[[Category: Cummons T]]
-[[Category: Jin, G.]]
+[[Category: Du M]]
-[[Category: Laakso, L M.]]
+[[Category: Jin G]]
-[[Category: Levin, J I.]]
+[[Category: Laakso LM]]
-[[Category: Schmid, J.]]
+[[Category: Levin JI]]
-[[Category: Skotnicki, J S.]]
+[[Category: Schmid J]]
-[[Category: Xu, J.]]
+[[Category: Skotnicki JS]]
-[[Category: Xu, W.]]
+[[Category: Xu J]]
-[[Category: Tace-inhibitor complex]]
+[[Category: Xu W]]
-[[Category: Tace/adam-17]]
-[[Category: Zn-endopeptidase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 03:34:14 2009''