2fv5: Difference between revisions

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-[[Image:2fv5.png|left|200px]]
-{{STRUCTURE_2fv5|  PDB=2fv5  |  SCENE=  }}
+==Crystal structure of TACE in complex with IK682==
+<StructureSection load='2fv5' size='340' side='right'caption='[[2fv5]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2fv5]] 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=2FV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FV5 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]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=541:(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE'>541</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=2fv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fv5 OCA], [https://pdbe.org/2fv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fv5 RCSB], [https://www.ebi.ac.uk/pdbsum/2fv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fv5 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/fv/2fv5_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=2fv5 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+TNFalpha converting enzyme (TACE) is the major metalloproteinase for the processing of TNFalpha, a key inflammatory cytokine. IK682, a hydroxamate compound, was reported to be a potent and specific TACE inhibitor [J.J. Duan, L. Chen, Z.R. Wasserman, Z. Lu, R.Q. Liu, M.B. Covington, M. Qian, K.D. Hardman, R.L. Magolda, R.C. Newton, D.D. Christ, R.R. Wexler, C.P. Decicco, J. Med. Chem. 45 (2002) 4954-4957]. The binding kinetics of IK682 and the ectodomain of human TACE was examined. The k(on) of IK682 was determined as 1.1+/-0.3 x 10(8) M(-1) min(-1). No detectable dissociation of IK682 from TACE was observed following dialysis, dilution, and extensive washing over a maximum of 72 h. This was in contrast to the rapid dissociation of IK682 from ADAM10. LC/MS analysis of the TACE-IK682 complex after dissociation under denaturing conditions indicated that the tight binding is not due to covalent interaction. The X-ray crystal structure of TACE-IK682 complex revealed multiple binding points at the S1' and S3' sites and the movement of a loop (from Ala349 to Gly442) to accommodate the binding of the quinolinyl group of IK682 at the S3' pocket. The conformational changes of TACE may contribute significantly to the high affinity binding as a result of a more stable TACE-inhibitor complex.
-===Crystal structure of TACE in complex with IK682===
+IK682, a tight binding inhibitor of TACE.,Niu X, Umland S, Ingram R, Beyer BM, Liu YH, Sun J, Lundell D, Orth P Arch Biochem Biophys. 2006 Jul 1;451(1):43-50. Epub 2006 May 5. PMID:16762314<ref>PMID:16762314</ref>
-{{ABSTRACT_PUBMED_16762314}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2fv5" style="background-color:#fffaf0;"></div>
-[[2fv5]] is a 2 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=2FV5 OCA].
 ==See Also==
-*[[A Disintegrin And Metalloproteinase|A Disintegrin And Metalloproteinase]]
+*[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:016762314</ref><references group="xtra"/>
+__TOC__
-[[Category: ADAM 17 endopeptidase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Niu, X.]]
+[[Category: Large Structures]]
-[[Category: Orth, P.]]
+[[Category: Niu X]]
-[[Category: Hydrolase]]
+[[Category: Orth P]]
-[[Category: Tace adam17 zn-endopeptidase]]