3cki

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{{Seed}}
 
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[[Image:3cki.jpg|left|200px]]
 
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==Crystal structure of the TACE-N-TIMP-3 complex==
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The line below this paragraph, containing "STRUCTURE_3cki", creates the "Structure Box" on the page.
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<StructureSection load='3cki' size='340' side='right'caption='[[3cki]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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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'>[[3cki]] 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=3CKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CKI 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]] 2.3&#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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3cki| PDB=3cki | 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=3cki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cki OCA], [https://pdbe.org/3cki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cki RCSB], [https://www.ebi.ac.uk/pdbsum/3cki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cki 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/ck/3cki_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=3cki 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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TIMP-3 (tissue inhibitor of metalloproteinases 3) is unique among the TIMP inhibitors, in that it effectively inhibits the TNF-alpha converting enzyme (TACE). In order to understand this selective capability of inhibition, we crystallized the complex formed by the catalytic domain of recombinant human TACE and the N-terminal domain of TIMP-3 (N-TIMP-3), and determined its molecular structure with X-ray data to 2.3 A resolution. The structure reveals that TIMP-3 exhibits a fold similar to those of TIMP-1 and TIMP-2, and interacts through its functional binding edge, which consists of the N-terminal segment and other loops, with the active-site cleft of TACE in a manner similar to that of matrix metalloproteinases (MMPs). Therefore, the mechanism of TIMP-3 binding toward TACE is not fundamentally different from that previously elucidated for the MMPs. The Phe34 phenyl side chain situated at the tip of the relatively short sA-sB loop of TIMP-3 extends into a unique hydrophobic groove of the TACE surface, and two Leu residues in the adjacent sC-connector and sE-sF loops are tightly packed in the interface allowing favourable interactions, in agreement with predictions obtained by systematic mutations by Gillian Murphy's group. The combination of favourable functional epitopes together with a considerable flexibility renders TIMP-3 an efficient TACE inhibitor. This structure might provide means to design more efficient TIMP inhibitors of TACE.
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===Crystal structure of the TACE-N-TIMP-3 complex===
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Structural determinants of the ADAM inhibition by TIMP-3: crystal structure of the TACE-N-TIMP-3 complex.,Wisniewska M, Goettig P, Maskos K, Belouski E, Winters D, Hecht R, Black R, Bode W J Mol Biol. 2008 Sep 19;381(5):1307-19. Epub 2008 Jul 7. PMID:18638486<ref>PMID:18638486</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 3cki" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18638486}}, 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 18638486 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18638486}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Sorsby fundus dystrophy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188826 188826]]
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==About this Structure==
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3CKI is a [[Protein complex]] 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=3CKI OCA].
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==Reference==
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Structural Determinants of the ADAM Inhibition by TIMP-3: Crystal Structure of the TACE-N-TIMP-3 Complex., Wisniewska M, Goettig P, Maskos K, Belouski E, Winters D, Hecht R, Black R, Bode W, J Mol Biol. 2008 Jul 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18638486 18638486]
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[[Category: ADAM 17 endopeptidase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Belouski, E.]]
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[[Category: Belouski E]]
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[[Category: Black, R.]]
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[[Category: Black R]]
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[[Category: Bode, W.]]
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[[Category: Bode W]]
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[[Category: Goettig, P.]]
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[[Category: Goettig P]]
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[[Category: Hecht, R.]]
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[[Category: Hecht R]]
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[[Category: Maskos, K.]]
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[[Category: Maskos K]]
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[[Category: Winters, D.]]
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[[Category: Winters D]]
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[[Category: Wisniewska, M.]]
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[[Category: Wisniewska M]]
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[[Category: Alternative splicing]]
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[[Category: Catalytic zinc]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Disease mutation]]
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[[Category: Extra-cellular matrix]]
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[[Category: Extracellular matrix]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase inhibitor]]
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[[Category: Membrane]]
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[[Category: Metal-binding]]
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[[Category: Metalloenzyme inhibitor]]
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[[Category: Metalloprotease]]
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[[Category: Metalloprotease inhibitor]]
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[[Category: Notch signaling pathway]]
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[[Category: Phosphoprotein]]
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[[Category: Protease]]
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[[Category: Sa-sb loop]]
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[[Category: Secreted]]
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[[Category: Sensory transduction]]
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[[Category: Sh3-binding]]
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[[Category: Transmembrane]]
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[[Category: Vision]]
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[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 6 12:58:47 2008''
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Current revision

Crystal structure of the TACE-N-TIMP-3 complex

PDB ID 3cki

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