8deg
From Proteopedia
(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]] 2.79Å</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. | ||
| - | + | ==See Also== | |
| - | + | *[[Mitogen-activated protein kinase kinase kinase|Mitogen-activated protein kinase kinase kinase]] | |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of DLK in complex with inhibitor DN0011197
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