3rtp | pdb_00003rtp
Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration
Template:ABSTRACT PUBMED 21813278
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]
About this Structure
3rtp is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Proteopedia Page Contributors and Editors (what is this?)
- Homo sapiens
- Mitogen-activated protein kinase
- Artis, D R.
- Bard, F.
- Bowers, S.
- Chan, W.
- Chen, L.
- Dryer, M.
- Galemmo, R A.
- Goldbach, E.
- Griswold-Prenne, I.
- Hom, R K.
- Konradi, A W.
- Lin, M.
- Lorentzen, C.
- Neitz, R J.
- Pan, H.
- Peterson, B.
- Powell, K.
- Probst, G D.
- Quincy, Q.
- Quinn, K P.
- Ren, Z.
- Ruslim, L.
- Samant, B.
- Sauer, J.
- Sealy, J M.
- Sham, H L.
- Tonn, G.
- Truong, A P.
- Wong, K.
- Wright, S.
- Yao, N.
- Yednock, T A.
- Zhang, H.
- Zmolek, W.
- Jnk inhibitor
- Neurodegeneration
- Pharmacokinetic property
- Transferase-transferase inhibitor complex
