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4z9l

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Revision as of 07:12, 19 June 2019

THE STRUCTURE OF JNK3 IN COMPLEX WITH AN IMIDAZOLE-PYRIMIDINE INHIBITOR

Structural highlights

4z9l is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 1pmq. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1pmq
Gene:	MAPK10, JNK3, JNK3A, PRKM10, SAPK1B (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]

Publication Abstract from PubMed

The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.

The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity.,Scapin G, Patel SB, Lisnock J, Becker JW, LoGrasso PV Chem Biol. 2003 Aug;10(8):705-12. PMID:12954329^[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
↑ Scapin G, Patel SB, Lisnock J, Becker JW, LoGrasso PV. The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. Chem Biol. 2003 Aug;10(8):705-12. PMID:12954329

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4z9l"

@@ Line 1: / Line 1: @@
 ==THE STRUCTURE OF JNK3 IN COMPLEX WITH AN IMIDAZOLE-PYRIMIDINE INHIBITOR==
-<StructureSection load='4z9l' size='340' side='right' caption='[[4z9l]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='4z9l' size='340' side='right'caption='[[4z9l]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4z9l]] is a 1 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1pmq 1pmq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z9L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z9L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4z9l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1pmq 1pmq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z9L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z9L FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=880:CYCLOHEXYL-{4-[5-(3,4-DICHLOROPHENYL)-2-PIPERIDIN-4-YL-3-PROPYL-3H-IMIDAZOL-4-YL]-PYRIMIDIN-2-YL}AMINE'>880</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pmq|1pmq]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK10, JNK3, JNK3A, PRKM10, SAPK1B ([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=4z9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z9l OCA], [http://pdbe.org/4z9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z9l RCSB], [http://www.ebi.ac.uk/pdbsum/4z9l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z9l ProSAT]</span></td></tr>
@@ Line 29: / Line 30: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Mitogen-activated protein kinase]]
 [[Category: Becker, J W]]
@@ Line 41: / Line 44: @@
 [[Category: Map kinase]]
 [[Category: Transferase]]
+[[Category: Transferase-inhibitor complex]]

4z9l

From Proteopedia

Revision as of 07:12, 19 June 2019

THE STRUCTURE OF JNK3 IN COMPLEX WITH AN IMIDAZOLE-PYRIMIDINE INHIBITOR

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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