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2p33

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Revision as of 09:17, 18 October 2017

Synthesis and SAR of Aminopyrimidines as Novel c-Jun N-Terminal Kinase (JNK) Inhibitors

Structural highlights

2p33 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	MAPK10, JNK3, JNK3A, PRKM10 (HUMAN)
Activity:	Mitogen-activated protein kinase, with EC number 2.7.11.24
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]

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 development of a series of novel aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay are discussed.

Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors.,Alam M, Beevers RE, Ceska T, Davenport RJ, Dickson KM, Fortunato M, Gowers L, Haughan AF, James LA, Jones MW, Kinsella N, Lowe C, Meissner JW, Nicolas AL, Perry BG, Phillips DJ, Pitt WR, Platt A, Ratcliffe AJ, Sharpe A, Tait LJ Bioorg Med Chem Lett. 2007 Jun 15;17(12):3463-7. Epub 2007 Mar 30. PMID:17459703^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ Alam M, Beevers RE, Ceska T, Davenport RJ, Dickson KM, Fortunato M, Gowers L, Haughan AF, James LA, Jones MW, Kinsella N, Lowe C, Meissner JW, Nicolas AL, Perry BG, Phillips DJ, Pitt WR, Platt A, Ratcliffe AJ, Sharpe A, Tait LJ. Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3463-7. Epub 2007 Mar 30. PMID:17459703 doi:10.1016/j.bmcl.2007.03.078

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p33"

@@ Line 1: / Line 1: @@
 ==Synthesis and SAR of Aminopyrimidines as Novel c-Jun N-Terminal Kinase (JNK) Inhibitors==
 <StructureSection load='2p33' size='340' side='right' caption='[[2p33]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK10, JNK3, JNK3A, PRKM10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p33 OCA], [http://pdbe.org/2p33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p33 RCSB], [http://www.ebi.ac.uk/pdbsum/2p33 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p33 OCA], [http://pdbe.org/2p33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p33 RCSB], [http://www.ebi.ac.uk/pdbsum/2p33 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p33 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 2p33" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
 == References ==
 <references/>

2p33

From Proteopedia

Revision as of 09:17, 18 October 2017

Synthesis and SAR of Aminopyrimidines as Novel c-Jun N-Terminal Kinase (JNK) Inhibitors

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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