3tti

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

DiseaseDisease

[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.

FunctionFunction

[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]

About this StructureAbout this Structure

3tti is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

^{[xtra 1]}

↑ Plantevin Krenitsky V, Nadolny L, Delgado M, Ayala L, Clareen SS, Hilgraf R, Albers R, Hegde S, D'Sidocky N, Sapienza J, Wright J, McCarrick M, Bahmanyar S, Chamberlain P, Delker SL, 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 MA, Benish B, Bodine T, Blease K, Raymon H, Cathers BE, Satoh Y. Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1433-8. Epub 2011 Dec 10. PMID:22244937 doi:10.1016/j.bmcl.2011.12.027

↑ 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

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OCA

[2] Plantevin Krenitsky V, Nadolny L, Delgado M, Ayala L, Clareen SS, Hilgraf R, Albers R, Hegde S, D'Sidocky N, Sapienza J, Wright J, McCarrick M, Bahmanyar S, Chamberlain P, Delker SL, 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 MA, Benish B, Bodine T, Blease K, Raymon H, Cathers BE, Satoh Y. Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1433-8. Epub 2011 Dec 10. PMID:22244937 doi:10.1016/j.bmcl.2011.12.027

[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

[1]

[xtra 1]