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'''Unreleased structure'''


The entry 3tti is ON HOLD
==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==
<StructureSection load='3tti' size='340' side='right'caption='[[3tti]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tti]] 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=3TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TTI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</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=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [https://pdbe.org/3tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [https://www.ebi.ac.uk/pdbsum/3tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti 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>


Authors: Plantevin-Krenitsky, V., Nadolny, L., Delgado, M., Ayala, L., Clareen, S., Hilgraf, R., Albers, R., Hegde, S., D'Sidocky, N., Sapienza, J., Wright, J., McCarrick, M., Bahmanyar, S., Chamberlain, P., Delker, S.L., Muir, J., Giegel, D., Xu, L., Celeridad, M., Lachowitzer, J., Bennett, B., Moghaddam, M., Khatsenko, O., Katz, J., Fan, R., Bai, A., Tang, Y., Shirley, M.A., Benish, B., Bodine, T., Blease, K., Raymon, H., Cathers, B.E., Satoh, Y.
==See Also==
 
*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
Description: Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Albers R]]
[[Category: Ayala L]]
[[Category: Bahmanyar S]]
[[Category: Bai A]]
[[Category: Benish B]]
[[Category: Bennett B]]
[[Category: Blease K]]
[[Category: Bodine T]]
[[Category: Cathers BE]]
[[Category: Celeridad M]]
[[Category: Chamberlain P]]
[[Category: Clareen S]]
[[Category: D'Sidocky N]]
[[Category: Delgado M]]
[[Category: Delker SL]]
[[Category: Fan R]]
[[Category: Giegel D]]
[[Category: Hegde S]]
[[Category: Hilgraf R]]
[[Category: Katz J]]
[[Category: Khatsenko O]]
[[Category: Lachowitzer J]]
[[Category: McCarrick M]]
[[Category: Moghaddam M]]
[[Category: Muir J]]
[[Category: Nadolny L]]
[[Category: Plantevin-Krenitsky V]]
[[Category: Raymon H]]
[[Category: Sapienza J]]
[[Category: Satoh Y]]
[[Category: Shirley MA]]
[[Category: Tang Y]]
[[Category: Wright J]]
[[Category: Xu L]]

Latest revision as of 13:11, 1 March 2024

Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitorCrystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor

Structural highlights

3tti is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MK10_HUMAN Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM: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

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.[1]

See Also

References

  1. ↑ Neidhart S, Antonsson B, Gillieron C, Vilbois F, Grenningloh G, Arkinstall S. c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10. FEBS Lett. 2001 Nov 16;508(2):259-64. PMID:11718727

3tti, resolution 2.20Å

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