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2waj

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Revision as of 08:57, 26 September 2018

Crystal structure of human Jnk3 complexed with a 1-aryl-3,4- dihydroisoquinoline inhibitor

Structural highlights

2waj 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:
Related:	1pmv, 1pmq, 1jnk, 1pmu, 1pmn
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 series of 1-aryl-3,4-dihydroisoquinoline inhibitors of JNK3 are described. Compounds 20 and 24 are the most potent inhibitors (pIC50 7.3 and 6.9, respectively in a radiometric filter binding assay), with 10- and 1000-fold selectivity over JNK2 and JNK1, respectively, and selectivity within the wider mitogen-activated protein kinase (MAPK) family against p38alpha and ERK2. X-ray crystallography of 16 reveals a highly unusual binding mode where an H-bond acceptor interaction with the hinge region is made by a chloro substituent.

1-Aryl-3,4-dihydroisoquinoline inhibitors of JNK3.,Christopher JA, Atkinson FL, Bax BD, Brown MJ, Champigny AC, Chuang TT, Jones EJ, Mosley JE, Musgrave JR Bioorg Med Chem Lett. 2009 Apr 15;19(8):2230-4. Epub 2009 Feb 28. PMID:19303774^[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
↑ Christopher JA, Atkinson FL, Bax BD, Brown MJ, Champigny AC, Chuang TT, Jones EJ, Mosley JE, Musgrave JR. 1-Aryl-3,4-dihydroisoquinoline inhibitors of JNK3. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2230-4. Epub 2009 Feb 28. PMID:19303774 doi:10.1016/j.bmcl.2009.02.098

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF HUMAN JNK3 COMPLEXED WITH A 1-ARYL-3,4-DIHYDROISOQUINOLINE INHIBITOR==
+==Crystal structure of human Jnk3 complexed with a 1-aryl-3,4- dihydroisoquinoline inhibitor==
 <StructureSection load='2waj' size='340' side='right' caption='[[2waj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pmv|1pmv]], [[1pmq|1pmq]], [[1jnk|1jnk]], [[1pmu|1pmu]], [[1pmn|1pmn]]</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=2waj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2waj OCA], [http://pdbe.org/2waj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2waj RCSB], [http://www.ebi.ac.uk/pdbsum/2waj 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=2waj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2waj OCA], [http://pdbe.org/2waj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2waj RCSB], [http://www.ebi.ac.uk/pdbsum/2waj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2waj ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wa/2waj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wa/2waj_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2waj

From Proteopedia

Revision as of 08:57, 26 September 2018

Crystal structure of human Jnk3 complexed with a 1-aryl-3,4- dihydroisoquinoline inhibitor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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