8deg: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8deg]] 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=8DEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DEG FirstGlance]. <br>
<table><tr><td colspan='2'>[[8deg]] 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=8DEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DEG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIQ:methyl+(1S,4S)-5-{(4P)-4-[5-amino-6-(difluoromethoxy)pyrazin-2-yl]-6-[(1R,4R)-2-azabicyclo[2.1.1]hexan-2-yl]pyridin-2-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate'>SIQ</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIQ:methyl+(1S,4S)-5-{(4P)-4-[5-amino-6-(difluoromethoxy)pyrazin-2-yl]-6-[(1R,4R)-2-azabicyclo[2.1.1]hexan-2-yl]pyridin-2-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate'>SIQ</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=8deg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8deg OCA], [https://pdbe.org/8deg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8deg RCSB], [https://www.ebi.ac.uk/pdbsum/8deg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8deg ProSAT]</span></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=8deg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8deg OCA], [https://pdbe.org/8deg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8deg RCSB], [https://www.ebi.ac.uk/pdbsum/8deg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8deg ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
[https://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dual leucine zipper kinase (DLK) and leucine zipper-bearing kinase (LZK) are regulators of neuronal degeneration and axon growth. Therefore, there is a considerable interest in developing DLK/LZK inhibitors for neurodegenerative diseases. Herein, we use ligand- and structure-based drug design approaches for identifying novel amino-pyrazine inhibitors of DLK/LZK. DN-1289 (14), a potent and selective dual DLK/LZK inhibitor, demonstrated excellent in vivo plasma half-life across species and is anticipated to freely penetrate the central nervous system with no brain impairment based on in vivo rodent pharmacokinetic studies and human in vitro transporter data. Proximal target engagement and disease relevant pathway biomarkers were also favorably regulated in an in vivo model of amyotrophic lateral sclerosis.


Discovery of Potent and Selective Dual Leucine Zipper Kinase/Leucine Zipper-Bearing Kinase Inhibitors with Neuroprotective Properties in In Vitro and In Vivo Models of Amyotrophic Lateral Sclerosis.,Craig RA 2nd, Fox BM, Hu C, Lexa KW, Osipov M, Thottumkara AP, Larhammar M, Miyamoto T, Rana A, Kane LA, Yulyaningsih E, Solanoy H, Nguyen H, Chau R, Earr T, Kajiwara Y, Fleck D, Lucas A, Haddick PCG, Takahashi RH, Tong V, Wang J, Canet MJ, Poda SB, Scearce-Levie K, Srivastava A, Sweeney ZK, Xu M, Zhang R, He J, Lei Y, Zhuo Z, de Vicente J J Med Chem. 2022 Dec 5. doi: 10.1021/acs.jmedchem.2c01056. PMID:36469401<ref>PMID:36469401</ref>
==See Also==
 
*[[Mitogen-activated protein kinase kinase kinase|Mitogen-activated protein kinase kinase kinase]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8deg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 10:25, 3 April 2024

Crystal structure of DLK in complex with inhibitor DN0011197Crystal structure of DLK in complex with inhibitor DN0011197

Structural highlights

8deg is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.79Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

M3K12_HUMAN May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.

See Also

8deg, resolution 2.79Å

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