2zdt

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{{Seed}}
 
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[[Image:2zdt.png|left|200px]]
 
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==Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor==
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The line below this paragraph, containing "STRUCTURE_2zdt", creates the "Structure Box" on the page.
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<StructureSection load='2zdt' size='340' side='right'caption='[[2zdt]], [[Resolution|resolution]] 2.00&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'>[[2zdt]] is a 1 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=2ZDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZDT 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&#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=46C:4-[(6-CHLORO-1-OXO-4-PHENYL-3-PROPANOYLISOQUINOLIN-2(1H)-YL)METHYL]BENZOIC+ACID'>46C</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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{{STRUCTURE_2zdt| PDB=2zdt | 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=2zdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zdt OCA], [https://pdbe.org/2zdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zdt RCSB], [https://www.ebi.ac.uk/pdbsum/2zdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zdt ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[https://omim.org/entry/606369 606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
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== Function ==
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[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</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/zd/2zdt_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2zdt 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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3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographic analysis of the complex between the isoquinolone compound and JNK3, as wells as the relationship between compound lipophilicity (logD) and activity in a cell-based assay. The compounds prepared showed potent JNK1 inhibitory activities in a cell-based assay. Among them the isoquinolone derivative possessing 5-[(cyclopropylamino)carbonyl]-1-methyl-1H-pyrazole (16e) exhibited significant anti-hypertrophic activity at doses of more than 1mg/kg (po) in a pressure-overload model.
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===Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor===
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Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (2).,Asano Y, Kitamura S, Ohra T, Itoh F, Kajino M, Tamura T, Kaneko M, Ikeda S, Igata H, Kawamoto T, Sogabe S, Matsumoto S, Tanaka T, Yamaguchi M, Kimura H, Fukumoto S Bioorg Med Chem. 2008 Apr 15;16(8):4699-714. Epub 2008 Feb 13. PMID:18313930<ref>PMID:18313930</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 2zdt" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18313930}}, adds the Publication Abstract to the page
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*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18313930 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18313930}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2ZDT is a 1 chain structure of 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=2ZDT OCA].
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==Reference==
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<ref group="xtra">PMID:18313930</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Mitogen-activated protein kinase]]
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[[Category: Large Structures]]
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[[Category: Asano, Y.]]
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[[Category: Asano Y]]
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[[Category: Fujishima, A.]]
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[[Category: Fujishima A]]
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[[Category: Fukumoto, S.]]
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[[Category: Fukumoto S]]
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[[Category: Habuka, N.]]
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[[Category: Habuka N]]
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[[Category: Sogabe, S.]]
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[[Category: Sogabe S]]
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[[Category: Alternative splicing]]
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[[Category: Atp-binding]]
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[[Category: Chromosomal rearrangement]]
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[[Category: Cytoplasm]]
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[[Category: Epilepsy]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Protein kinase]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 01:59:47 2009''
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Current revision

Crystal Structure of human JNK3 complexed with an isoquinolone inhibitor

PDB ID 2zdt

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