4e73
From Proteopedia
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==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor== | ==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor== | ||
| - | <StructureSection load='4e73' size='340' side='right' caption='[[4e73]], [[Resolution|resolution]] 2.27Å' scene=''> | + | <StructureSection load='4e73' size='340' side='right'caption='[[4e73]], [[Resolution|resolution]] 2.27Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4e73]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E73 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene></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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [https://pdbe.org/4e73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [https://www.ebi.ac.uk/pdbsum/4e73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e73 ProSAT]</span></td></tr> | |
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref> | ||
== Function == | == Function == | ||
| - | [[ | + | [[https://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation 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 MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
| - | *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | + | *[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Janson | + | [[Category: Janson CA]] |
| - | [[Category: Lukacs | + | [[Category: Lukacs CM]] |
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Revision as of 06:54, 28 September 2022
Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor
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