4twc: Difference between revisions
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==2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4- carboxamide derivatives as potent inhibitors of CK1d/e== | ==2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4- carboxamide derivatives as potent inhibitors of CK1d/e== | ||
<StructureSection load='4twc' size='340' side='right' caption='[[4twc]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='4twc' size='340' side='right'caption='[[4twc]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4twc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TWC OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4twc]] is a 2 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=4TWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TWC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=37J:2-{[2-(TRIFLUOROMETHOXY)BENZOYL]AMINO}-N-[6-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-2-YL]-1,3-THIAZOLE-4-CARBOXAMIDE'>37J</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.7Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=37J:2-{[2-(TRIFLUOROMETHOXY)BENZOYL]AMINO}-N-[6-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-2-YL]-1,3-THIAZOLE-4-CARBOXAMIDE'>37J</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4twc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twc OCA], [https://pdbe.org/4twc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4twc RCSB], [https://www.ebi.ac.uk/pdbsum/4twc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4twc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Casein kinase|Casein kinase]] | *[[Casein kinase 3D structures|Casein kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bischof | [[Category: Homo sapiens]] | ||
[[Category: Grothey | [[Category: Large Structures]] | ||
[[Category: Knippschild | [[Category: Bischof J]] | ||
[[Category: Leban | [[Category: Grothey A]] | ||
[[Category: Othersen | [[Category: Knippschild U]] | ||
[[Category: Radunsky | [[Category: Leban L]] | ||
[[Category: Strobl | [[Category: Othersen O]] | ||
[[Category: Vitt | [[Category: Radunsky B]] | ||
[[Category: Zaja | [[Category: Strobl S]] | ||
[[Category: Vitt D]] | |||
[[Category: Zaja M]] | |||