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3lgp
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of catalytic domain of tace with benzimidazolyl-thienyl-tartrate based inhibitor== | |
| + | <StructureSection load='3lgp' size='340' side='right'caption='[[3lgp]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3lgp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LGP FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=50X:(2R,3R)-4-[(2R)-2-(3-CHLOROPHENYL)PYRROLIDIN-1-YL]-2,3-DIHYDROXY-4-OXO-N-[(5-{[2-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-1-YL]METHYL}THIOPHEN-2-YL)METHYL]BUTANAMIDE'>50X</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bkc|1bkc]], [[3kmc|3kmc]], [[3kme|3kme]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAM17, CSVP, TACE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/ADAM_17_endopeptidase ADAM 17 endopeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.86 3.4.24.86] </span></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=3lgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lgp OCA], [https://pdbe.org/3lgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lgp RCSB], [https://www.ebi.ac.uk/pdbsum/3lgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lgp 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/lg/3lgp_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3lgp ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The syntheses and structure-activity relationships of the tartrate-based TACE inhibitors are discussed. The optimization of both the prime and non-prime sites led to compounds with picomolar activity. Several analogs demonstrated good rat pharmacokinetics. | ||
| - | + | Structure and activity relationships of tartrate-based TACE inhibitors.,Li D, Popovici-Muller J, Belanger DB, Caldwell J, Dai C, David M, Girijavallabhan VM, Lavey BJ, Lee JF, Liu Z, Mazzola R, Rizvi R, Rosner KE, Shankar B, Spitler J, Ting PC, Vaccaro H, Yu W, Zhou G, Zhu Z, Niu X, Sun J, Guo Z, Orth P, Chen S, Kozlowski JA, Lundell DJ, Madison V, McKittrick B, Piwinski JJ, Shih NY, Shipps GW Jr, Siddiqui MA, Strickland CO Bioorg Med Chem Lett. 2010 Aug 15;20(16):4812-5. Epub 2010 Jun 25. PMID:20638281<ref>PMID:20638281</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3lgp" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: ADAM 17 endopeptidase]] | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Orth, P]] | ||
| + | [[Category: Cleavage on pair of basic residue]] | ||
| + | [[Category: Disulfide bond]] | ||
| + | [[Category: Glycoprotein]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Membrane]] | ||
| + | [[Category: Metal-binding]] | ||
| + | [[Category: Metalloprotease]] | ||
| + | [[Category: Notch signaling pathway]] | ||
| + | [[Category: Phosphoprotein]] | ||
| + | [[Category: Protease]] | ||
| + | [[Category: Sh3-binding]] | ||
| + | [[Category: Transmembrane]] | ||
| + | [[Category: Zymogen]] | ||
Current revision
Crystal structure of catalytic domain of tace with benzimidazolyl-thienyl-tartrate based inhibitor
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