2r9s

c-Jun N-terminal Kinase 3 with 3,5-Disubstituted Quinoline inhibitorc-Jun N-terminal Kinase 3 with 3,5-Disubstituted Quinoline inhibitor

Structural highlights 2r9s is a 2 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 2.4Å 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The structure-based design and synthesis of a novel series of c-Jun N-terminal kinase (JNK) inhibitors with selectivity against p38 is reported. The unique structure of 3,5-disubstituted quinolines (2) was developed from the previously reported 4-(2,7-phenanthrolin-9-yl)phenol (1). The X-ray crystal structure of 16a in JNK3 reveals an unexpected binding mode for this new scaffold with protein. 3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors.,Jiang R, Duckett D, Chen W, Habel J, Ling YY, LoGrasso P, Kamenecka TM Bioorg Med Chem Lett. 2007 Nov 15;17(22):6378-82. Epub 2007 Aug 26. PMID:17911023 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mitogen-activated protein kinase 3D structures

spinqualitylabelsall models 2r9s, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image