View source for 3ttj


==Crystal Structure of JNK3 complexed with CC-359, a JNK inhibitor for the prevention of ischemia-reperfusion injury==
<StructureSection load='3ttj' size='340' side='right'caption='[[3ttj]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ttj]] is a 1 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=3TTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TTJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JBI:9-CYCLOPENTYL-N~8~-(2-FLUOROPHENYL)-N~2~-(4-METHOXYPHENYL)-9H-PURINE-2,8-DIAMINE'>JBI</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;'>[[3tti|3tti]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK10, JNK3, JNK3A, PRKM10 ([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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3ttj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ttj OCA], [https://pdbe.org/3ttj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ttj RCSB], [https://www.ebi.ac.uk/pdbsum/3ttj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ttj ProSAT]</span></td></tr>
</table>
== Disease ==
[[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. 
== Function ==
[[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.

Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury.,Krenitsky VP, Delgado M, Nadolny L, Sahasrabudhe K, Ayala L, Clareen SS, Hilgraf R, Albers R, Kois A, Hughes K, Wright J, Nowakowski J, Sudbeck E, Ghosh S, Bahmanyar S, Chamberlain P, Muir J, Cathers BE, Giegel D, Xu L, Celeridad M, Moghaddam M, Khatsenko O, Omholt P, Katz J, Pai S, Fan R, Tang Y, Shirley MA, Benish B, Blease K, Raymon H, Bhagwat S, Henderson I, Cole AG, Bennett B, Satoh Y Bioorg Med Chem Lett. 2011 Dec 11. PMID:22226655<ref>PMID:22226655</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ttj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Mitogen-activated protein kinase]]
[[Category: Albers, R]]
[[Category: Ayala, S]]
[[Category: Bahmanyar, S]]
[[Category: Benish, B]]
[[Category: Bennett, B]]
[[Category: Bhagwat, S]]
[[Category: Blease, K]]
[[Category: Cathers, B E]]
[[Category: Celeridad, M]]
[[Category: Chamberlain, P]]
[[Category: Clareen, S]]
[[Category: Delgado, M]]
[[Category: Fan, R]]
[[Category: Ghosh, S]]
[[Category: Giegel, D]]
[[Category: Hilgraf, R]]
[[Category: Hughes, K]]
[[Category: Katz, J]]
[[Category: Khatsenko, O]]
[[Category: Kois, A]]
[[Category: Moghaddam, M]]
[[Category: Muir, J]]
[[Category: Nadolny, L]]
[[Category: Nowakowski, J]]
[[Category: Omholt, P]]
[[Category: Pai, S]]
[[Category: Plantevin-Krenitsky, V]]
[[Category: Raymon, H]]
[[Category: Sahasrabudhe, K]]
[[Category: Satoh, Y]]
[[Category: Shirley, M A]]
[[Category: Sudbeck, E]]
[[Category: Tang, Y]]
[[Category: Wright, J]]
[[Category: Xu, L]]
[[Category: Jnk3]]
[[Category: Mitogen-activated protein kinase 10]]
[[Category: Protein kinase inhibitor]]
[[Category: Transferase-transferase inhibitor complex]]