3fv8

From Proteopedia

(Difference between revisions)

Revision as of 00:43, 16 November 2017

JNK3 bound to piperazine amide inhibitor, SR2774.

Structural highlights

3fv8 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:	,
NonStd Res:	,
Gene:	JNK3, JNK3A, MAPK10, 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

A novel series of c-jun N-terminal kinase (JNK) inhibitors were designed and developed from a high-throughput-screening hit. Through the optimization of the piperazine amide 1, several potent compounds were discovered. The X-ray crystal structure of 4g showed a unique binding mode different from other well known JNK3 inhibitors.

Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors.,Shin Y, Chen W, Habel J, Duckett D, Ling YY, Koenig M, He Y, Vojkovsky T, LoGrasso P, Kamenecka TM Bioorg Med Chem Lett. 2009 Jun 15;19(12):3344-7. Epub 2009 Mar 26. PMID:19433357^[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
↑ Shin Y, Chen W, Habel J, Duckett D, Ling YY, Koenig M, He Y, Vojkovsky T, LoGrasso P, Kamenecka TM. Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3344-7. Epub 2009 Mar 26. PMID:19433357 doi:10.1016/j.bmcl.2009.03.086

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/3fv8"

@@ Line 1: / Line 1: @@
 ==JNK3 bound to piperazine amide inhibitor, SR2774.==
 <StructureSection load='3fv8' size='340' side='right' caption='[[3fv8]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JNK3, JNK3A, MAPK10, 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=3fv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fv8 OCA], [http://pdbe.org/3fv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fv8 RCSB], [http://www.ebi.ac.uk/pdbsum/3fv8 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=3fv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fv8 OCA], [http://pdbe.org/3fv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fv8 RCSB], [http://www.ebi.ac.uk/pdbsum/3fv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fv8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 32: / Line 33: @@
 </div>
 <div class="pdbe-citations 3fv8" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
 == References ==
 <references/>
@@ Line 42: / Line 40: @@
 [[Category: Mitogen-activated protein kinase]]
 [[Category: Habel, J E]]
+[[Category: Alternative splicing]]
 [[Category: Atp-binding]]
+[[Category: Chromosomal rearrangement]]
+[[Category: Cytoplasm]]
 [[Category: Epilepsy]]
 [[Category: Jnk3]]

3fv8

From Proteopedia

Revision as of 00:43, 16 November 2017

JNK3 bound to piperazine amide inhibitor, SR2774.

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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