3g9n

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{{STRUCTURE_3g9n| PDB=3g9n | SCENE= }}
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==JNK3 bound to (Z)-1-((6-fluoro-4H-benzo[d][1,3]dioxin-8-yl)methyl)-3-(hydroxyimino)-4-phenylindolin-2-one==
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===JNK3 bound to (Z)-1-((6-fluoro-4H-benzo[d][1,3]dioxin-8-yl)methyl)-3-(hydroxyimino)-4-phenylindolin-2-one===
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<StructureSection load='3g9n' size='340' side='right' caption='[[3g9n]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19361991}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3g9n]] is a 1 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=3G9N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G9N FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J88:(3Z)-1-[(6-FLUORO-4H-1,3-BENZODIOXIN-8-YL)METHYL]-4-PHENYL-1H-INDOLE-2,3-DIONE+3-OXIME'>J88</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3g90|3g90]], [[3g9l|3g9l]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3g9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g9n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3g9n RCSB], [http://www.ebi.ac.uk/pdbsum/3g9n PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://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.
[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://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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[[http://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/g9/3g9n_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/chain_selection.php?pdb_ID=2ata 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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A series of N-benzylated isatin oximes were developed as inhibitors of the mitogen-activated kinase, JNK3. X-ray crystallographic structures aided in the design and synthesis of novel, selective compounds, that inhibit JNK3, but not p38 MAP kinase and provided key insights into understanding the behavior of gatekeeper residue methionine-146 in determining target selectivity for this series.
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==Function==
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Structure-based design and parallel synthesis of N-benzyl isatin oximes as JNK3 MAP kinase inhibitors.,Cao J, Gao H, Bemis G, Salituro F, Ledeboer M, Harrington E, Wilke S, Taslimi P, Pazhanisamy S, Xie X, Jacobs M, Green J Bioorg Med Chem Lett. 2009 May 15;19(10):2891-5. Epub 2009 Mar 17. PMID:19361991<ref>PMID:19361991</ref>
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[[http://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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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3g9n]] is a 1 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=3G9N OCA].
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</div>
==See Also==
==See Also==
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019361991</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Mitogen-activated protein kinase]]
[[Category: Mitogen-activated protein kinase]]
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[[Category: Jacobs, M D.]]
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[[Category: Jacobs, M D]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Epilepsy]]
[[Category: Epilepsy]]

Revision as of 13:34, 18 December 2014

JNK3 bound to (Z)-1-((6-fluoro-4H-benzo[d][1,3]dioxin-8-yl)methyl)-3-(hydroxyimino)-4-phenylindolin-2-one

3g9n, resolution 2.80Å

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