2waj

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (15:50, 13 December 2023) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_2waj| PDB=2waj | SCENE= }}
 
-
===CRYSTAL STRUCTURE OF HUMAN JNK3 COMPLEXED WITH A 1-ARYL-3,4-DIHYDROISOQUINOLINE INHIBITOR===
 
-
{{ABSTRACT_PUBMED_19303774}}
 
-
==Disease==
+
==Crystal structure of human Jnk3 complexed with a 1-aryl-3,4- dihydroisoquinoline inhibitor==
-
[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://omim.org/entry/606369 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.
+
<StructureSection load='2waj' size='340' side='right'caption='[[2waj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2waj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WAJ FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SNB:1-(3-BROMOPHENYL)-7-CHLORO-6-METHOXY-3,4-DIHYDROISOQUINOLINE'>SNB</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2waj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2waj OCA], [https://pdbe.org/2waj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2waj RCSB], [https://www.ebi.ac.uk/pdbsum/2waj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2waj ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[https://omim.org/entry/606369 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 ==
 +
[https://www.uniprot.org/uniprot/MK10_HUMAN 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.<ref>PMID:11718727</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<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>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2waj ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
==Function==
+
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<ref>PMID:19303774</ref>
-
[[http://www.uniprot.org/uniprot/MK10_HUMAN 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.<ref>PMID:11718727</ref>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[2waj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WAJ OCA].
+
</div>
 +
<div class="pdbe-citations 2waj" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
-
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
+
*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:019303774</ref><references group="xtra"/><references/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Mitogen-activated protein kinase]]
+
[[Category: Large Structures]]
-
[[Category: Bax, B D.]]
+
[[Category: Bax BD]]
-
[[Category: Christopher, J A.]]
+
[[Category: Christopher JA]]
-
[[Category: Jones, E J.]]
+
[[Category: Jones EJ]]
-
[[Category: Mosley, J E.]]
+
[[Category: Mosley JE]]
-
[[Category: Atp-binding]]
+
-
[[Category: Epilepsy]]
+
-
[[Category: Kinase]]
+
-
[[Category: Nucleotide-binding]]
+
-
[[Category: Phosphoprotein]]
+
-
[[Category: Protein kinase]]
+
-
[[Category: Serine/threonine-protein kinase]]
+
-
[[Category: Transferase]]
+

Current revision

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

PDB ID 2waj

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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