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==Crystal structure of the CK2alpha/compound3 complex== | ==Crystal structure of the CK2alpha/compound3 complex== | ||
<StructureSection load='3wil' size='340' side='right' caption='[[3wil]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='3wil' size='340' side='right'caption='[[3wil]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3wil]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WIL OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[3wil]] 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=3WIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WIL FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LCD:{[(2Z)-2-(3,4-DIMETHOXYBENZYLIDENE)-3-OXO-2,3-DIHYDRO-1-BENZOFURAN-6-YL]OXY}ACETIC+ACID'>LCD</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=3wil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wil OCA], [https://pdbe.org/3wil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wil RCSB], [https://www.ebi.ac.uk/pdbsum/3wil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wil ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Novel protein kinase CK2 inhibitors were identified using the solvent dipole ordering virtual screening method. A total of 26 compounds categorized in 15 distinct scaffold classes inhibited greater than 50% of enzyme activity at 50 muM, and eight exhibited IC50 values less than 10 muM. Most of the identified compounds are lead-like and dissimilar to known inhibitors. The crystal structures of two of the CK2 complexes revealed the high accuracy of the predicted binding modes. | |||
Identification of protein kinase CK2 inhibitors using solvent dipole ordering virtual screening.,Nakanishi I, Murata K, Nagata N, Kurono M, Kinoshita T, Yasue M, Miyazaki T, Takei Y, Nakamura S, Sakurai A, Iwamoto N, Nishiwaki K, Nakaniwa T, Sekiguchi Y, Hirasawa A, Tsujimoto G, Kitaura K Eur J Med Chem. 2015;96:396-404. doi: 10.1016/j.ejmech.2015.04.032. Epub 2015 Apr , 15. PMID:25912672<ref>PMID:25912672</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3wil" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Casein kinase 3D structures|Casein kinase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Kinoshita T]] | ||
[[Category: | [[Category: Nakanishi I]] | ||