3da6

From Proteopedia

(Difference between revisions)

Revision as of 08:45, 25 October 2017

Crystal Structure of human JNK3 complexed with N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)naphthalen-1-yl)-1H-benzo[d]imidazol-2-amine

Structural highlights

3da6 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:	2b1p
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

Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase.

Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase.,Cee VJ, Cheng AC, Romero K, Bellon S, Mohr C, Whittington DA, Bak A, Bready J, Caenepeel S, Coxon A, Deak HL, Fretland J, Gu Y, Hodous BL, Huang X, Kim JL, Lin J, Long AM, Nguyen H, Olivieri PR, Patel VF, Wang L, Zhou Y, Hughes P, Geuns-Meyer S Bioorg Med Chem Lett. 2009 Jan 15;19(2):424-7. Epub 2008 Nov 20. PMID:19062275^[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
↑ Cee VJ, Cheng AC, Romero K, Bellon S, Mohr C, Whittington DA, Bak A, Bready J, Caenepeel S, Coxon A, Deak HL, Fretland J, Gu Y, Hodous BL, Huang X, Kim JL, Lin J, Long AM, Nguyen H, Olivieri PR, Patel VF, Wang L, Zhou Y, Hughes P, Geuns-Meyer S. Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase. Bioorg Med Chem Lett. 2009 Jan 15;19(2):424-7. Epub 2008 Nov 20. PMID:19062275 doi:10.1016/j.bmcl.2008.11.056

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/3da6"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of human JNK3 complexed with N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)naphthalen-1-yl)-1H-benzo[d]imidazol-2-amine==
 <StructureSection load='3da6' size='340' side='right' caption='[[3da6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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=3da6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3da6 OCA], [http://pdbe.org/3da6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3da6 RCSB], [http://www.ebi.ac.uk/pdbsum/3da6 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=3da6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3da6 OCA], [http://pdbe.org/3da6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3da6 RCSB], [http://www.ebi.ac.uk/pdbsum/3da6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3da6 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 32: / Line 33: @@
 </div>
 <div class="pdbe-citations 3da6" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
 == References ==
 <references/>
@@ Line 60: / Line 58: @@
 [[Category: Wang, L]]
 [[Category: Whittington, D A]]
+[[Category: Alternative splicing]]
 [[Category: Atp-binding]]
+[[Category: Chromosomal rearrangement]]
+[[Category: Cytoplasm]]
 [[Category: Epilepsy]]
 [[Category: Jnk3]]

3da6

From Proteopedia

Revision as of 08:45, 25 October 2017

Crystal Structure of human JNK3 complexed with N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)naphthalen-1-yl)-1H-benzo[d]imidazol-2-amine

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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