1zxc

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{{Seed}}
 
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[[Image:1zxc.png|left|200px]]
 
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==Crystal structure of catalytic domain of TNF-alpha converting enzyme (TACE) with inhibitor==
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The line below this paragraph, containing "STRUCTURE_1zxc", creates the "Structure Box" on the page.
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<StructureSection load='1zxc' size='340' side='right'caption='[[1zxc]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1zxc]] 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=1ZXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZXC FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.28&#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=IH6:(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE'>IH6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1zxc| PDB=1zxc | SCENE= }}
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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=1zxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zxc OCA], [https://pdbe.org/1zxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zxc RCSB], [https://www.ebi.ac.uk/pdbsum/1zxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zxc ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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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/zx/1zxc_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=1zxc 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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The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.
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===Crystal structure of catalytic domain of TNF-alpha converting enzyme (TACE) with inhibitor===
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Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.,Levin JI, Chen JM, Laakso LM, Du M, Du X, Venkatesan AM, Sandanayaka V, Zask A, Xu J, Xu W, Zhang Y, Skotnicki JS Bioorg Med Chem Lett. 2005 Oct 1;15(19):4345-9. PMID:16084720<ref>PMID:16084720</ref>
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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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<div class="pdbe-citations 1zxc" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16084720}}, adds the Publication Abstract to the page
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*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 16084720 is the PubMed ID number.
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== References ==
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-->
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<references/>
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{{ABSTRACT_PUBMED_16084720}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1ZXC 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=1ZXC OCA].
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==Reference==
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<ref group="xtra">PMID:16084720</ref><references group="xtra"/>
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[[Category: ADAM 17 endopeptidase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Barone, D.]]
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[[Category: Large Structures]]
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[[Category: Chen, J M.]]
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[[Category: Barone D]]
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[[Category: Cowling, R.]]
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[[Category: Chen JM]]
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[[Category: Cummons, T.]]
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[[Category: Cowling R]]
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[[Category: Du, M.]]
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[[Category: Cummons T]]
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[[Category: Jin, G.]]
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[[Category: Du M]]
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[[Category: Laakso, L M.]]
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[[Category: Jin G]]
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[[Category: Levin, J I.]]
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[[Category: Laakso LM]]
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[[Category: Schmid, J.]]
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[[Category: Levin JI]]
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[[Category: Skotnicki, J S.]]
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[[Category: Schmid J]]
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[[Category: Xu, J.]]
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[[Category: Skotnicki JS]]
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[[Category: Xu, W.]]
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[[Category: Xu J]]
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[[Category: Zhang, Y.]]
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[[Category: Xu W]]
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[[Category: Tace-inhibitor complex]]
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[[Category: Zhang Y]]
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[[Category: Tace/adam-17]]
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[[Category: Zn-endopeptidase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 20:20:07 2009''
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Current revision

Crystal structure of catalytic domain of TNF-alpha converting enzyme (TACE) with inhibitor

PDB ID 1zxc

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