2b1p

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[[Image:2b1p.gif|left|200px]]<br /><applet load="2b1p" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2b1p, resolution 1.900&Aring;" />
 
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'''inhibitor complex of JNK3'''<br />
 
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==Overview==
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==inhibitor complex of JNK3==
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The structure-based design and synthesis of a new series of c-Jun N-terminal kinase-3 inhibitors with selectivity against JNK1 and p38alpha is reported. The novel series of substituted 6-anilinoindazoles were designed based on a combination of hits from high throughput screening and X-ray crystal structure information of the compounds crystallized into the JNK3 ATP binding active site.
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<StructureSection load='2b1p' size='340' side='right'caption='[[2b1p]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2b1p]] 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=2B1P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B1P FirstGlance]. <br>
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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]] 1.9&#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=AIZ:3-{6-[(2-CHLOROPHENYL)AMINO]-1H-INDAZOL-3-YL}-5-{[4-(DIMETHYLAMINO)BUTANOYL]AMINO}BENZOIC+ACID'>AIZ</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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=2b1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b1p OCA], [https://pdbe.org/2b1p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b1p RCSB], [https://www.ebi.ac.uk/pdbsum/2b1p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b1p 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/b1/2b1p_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=2b1p ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Epileptic encephalopathy, Lennox-Gastaut type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602897 602897]]
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*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2B1P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=AIZ:'>AIZ</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B1P OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3., Swahn BM, Huerta F, Kallin E, Malmstrom J, Weigelt T, Viklund J, Womack P, Xue Y, Ohberg L, Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16140012 16140012]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Huerta F]]
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[[Category: Huerta, F.]]
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[[Category: Kallin E]]
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[[Category: Kallin, E.]]
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[[Category: Malmstrom J]]
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[[Category: Malmstrom, J.]]
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[[Category: Ohberg L]]
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[[Category: Ohberg, L.]]
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[[Category: Swahn BM]]
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[[Category: Swahn, B M.]]
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[[Category: Viklund J]]
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[[Category: Viklund, J.]]
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[[Category: Weigelt T]]
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[[Category: Weigelt, T.]]
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[[Category: Womack P]]
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[[Category: Womack, P.]]
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[[Category: Xue Y]]
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[[Category: Xue, Y.]]
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[[Category: AIZ]]
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[[Category: BME]]
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[[Category: SO4]]
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[[Category: enzyme-inhibitor complex]]
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[[Category: kinase inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:33:17 2008''
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Current revision

inhibitor complex of JNK3

PDB ID 2b1p

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