3owk: Difference between revisions

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 ==Human CK2 catalytic domain in complex with a benzopyridoindole derivative inhibitor==
-<StructureSection load='3owk' size='340' side='right' caption='[[3owk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='3owk' size='340' side='right'caption='[[3owk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3owk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OWK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OWK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3owk]] 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=3OWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OWK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=18E:7-CHLORO-10-METHYL-11H-BENZO[G]PYRIDO[4,3-B]INDOL-3-OL'>18E</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]] 1.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mb6|3mb6]], [[3mb7|3mb7]], [[3owj|3owj]], [[3owl|3owl]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=18E:7-CHLORO-10-METHYL-11H-BENZO[G]PYRIDO[4,3-B]INDOL-3-OL'>18E</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSNK2A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3owk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3owk OCA], [https://pdbe.org/3owk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3owk RCSB], [https://www.ebi.ac.uk/pdbsum/3owk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3owk ProSAT]</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=3owk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3owk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3owk RCSB], [http://www.ebi.ac.uk/pdbsum/3owk PDBsum]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/CSK21_HUMAN CSK21_HUMAN] Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.<ref>PMID:11239457</ref> <ref>PMID:11704824</ref> <ref>PMID:16193064</ref> <ref>PMID:19188443</ref>
-The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2-inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. Cancer Res; 70(23); 9865-74. (c)2010 AACR.
-Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2.,Prudent R, Moucadel V, Nguyen CH, Barette C, Schmidt F, Florent JC, Lafanechere L, Sautel CF, Duchemin-Pelletier E, Spreux E, Filhol O, Reiser JB, Cochet C Cancer Res. 2010 Dec 1;70(23):9865-74. Epub 2010 Nov 30. PMID:21118972<ref>PMID:21118972</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+==See Also==
-</div>
+*[[Casein kinase 3D structures|Casein kinase 3D structures]]
 == References ==
 <references/>
@@ Line 21: / Line 18: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Cochet, C]]
+[[Category: Large Structures]]
-[[Category: Prudent, R]]
+[[Category: Cochet C]]
-[[Category: Reiser, J B]]
+[[Category: Prudent R]]
-[[Category: Benzopyridoindole]]
+[[Category: Reiser J-B]]
-[[Category: Ck2]]
-[[Category: Ellipticine]]
-[[Category: Inhibitor]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase]]
-[[Category: Transferase-transferase inhibitor complex]]