We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.
5vo2
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==DLK in complex with inhibitor 5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine (compound 7)== | |
| + | <StructureSection load='5vo2' size='340' side='right' caption='[[5vo2]], [[Resolution|resolution]] 2.96Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5vo2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VO2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VO2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9FV:5-{5-[1-(oxetan-3-yl)piperidin-4-yl]-1-(propan-2-yl)-1H-pyrazol-3-yl}-3-(trifluoromethyl)pyridin-2-amine'>9FV</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vo1|5vo1]]</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_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=5vo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vo2 OCA], [http://pdbe.org/5vo2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vo2 RCSB], [http://www.ebi.ac.uk/pdbsum/5vo2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vo2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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 == | ||
| + | Significant data exists to suggest that dual leucine zipper kinase (DLK, MAP3K12) is a conserved regulator of neuronal degeneration following neuronal injury and in chronic neurodegenerative disease. Consequently, there is considerable interest in the identification of DLK inhibitors with a profile compatible with development for these indications. Herein, we use structure-based drug design combined with a focus on CNS drug-like properties to generate compounds with superior kinase selectivity and metabolic stability as compared to previously disclosed DLK inhibitors. These compounds, exemplified by inhibitor 14, retain excellent CNS penetration and are well tolerated following multiple days of dosing at concentrations that exceed those required for DLK inhibition in the brain. | ||
| - | + | Selective Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12) with Activity in a Model of Alzheimer's Disease.,Patel S, Meilandt WJ, Erickson RI, Chen J, Deshmukh G, Estrada AA, Fuji RN, Gibbons P, Gustafson A, Harris SF, Imperio J, Liu W, Liu X, Liu Y, Lyssikatos JP, Ma C, Yin J, Lewcock JW, Siu M J Med Chem. 2017 Sep 20. doi: 10.1021/acs.jmedchem.7b00843. PMID:28929759<ref>PMID:28929759</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5vo2" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Mitogen-activated protein kinase kinase kinase]] | ||
| + | [[Category: HARRIS, S F]] | ||
| + | [[Category: YIN, J]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 09:27, 4 October 2017
DLK in complex with inhibitor 5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine (compound 7)
| |||||||||||
