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| | <StructureSection load='6l20' size='340' side='right'caption='[[6l20]], [[Resolution|resolution]] 3.09Å' scene=''> | | <StructureSection load='6l20' size='340' side='right'caption='[[6l20]], [[Resolution|resolution]] 3.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6l20]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L20 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6L20 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6l20]] is a 4 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=6L20 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L20 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E3U:(6aR)-3,4,6a,10-tetrakis(oxidanyl)-6,7-dihydroindeno[2,1-c]chromen-9-one'>E3U</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]] 3.0873513Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E3U:(6aR)-3,4,6a,10-tetrakis(oxidanyl)-6,7-dihydroindeno[2,1-c]chromen-9-one'>E3U</scene></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=6l20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l20 OCA], [http://pdbe.org/6l20 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l20 RCSB], [http://www.ebi.ac.uk/pdbsum/6l20 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l20 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=6l20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l20 OCA], [https://pdbe.org/6l20 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l20 RCSB], [https://www.ebi.ac.uk/pdbsum/6l20 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l20 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CSK22_HUMAN CSK22_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> | + | [https://www.uniprot.org/uniprot/CSK22_HUMAN CSK22_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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6l20" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6l20" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Casein kinase 3D structures|Casein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | [[Category: Kinoshita T]] |
| - | [[Category: Kinoshita, T]] | + | [[Category: Tsuyuguchi M]] |
| - | [[Category: Tsuyuguchi, M]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
CSK22_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.[1] [2] [3]
Publication Abstract from PubMed
Casein kinase 2 catalytic subunit (CK2alpha) is classified into two subtypes CK2alpha1 and CK2alpha2. CK2alpha1 is a drug discovery target, whereas CK2alpha2 is an off-target of CK2alpha1 inhibitors. High amino acid sequence homology between these subtypes hampers efforts to produce ATP competitive inhibitors that are highly selective to CK2alpha1. Hematein was identified previously as a non-ATP-competitive inhibitor for CK2alpha1, whereas this compound acts as an ATP competitive CK2alpha2 inhibitor. Crystal structures of CK2alpha1 and CK2alpha2 in complex with hematein revealed distinct binding features that provide structural insights for producing CK2alpha1-selective inhibitors.
Structural insights for producing CK2alpha1-specific inhibitors.,Tsuyuguchi M, Nakaniwa T, Hirasawa A, Nakanishi I, Kinoshita T Bioorg Med Chem Lett. 2020 Jan 15;30(2):126837. doi: 10.1016/j.bmcl.2019.126837. , Epub 2019 Dec 3. PMID:31859160[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H. A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell. 2001 Feb;7(2):283-92. PMID:11239457
- ↑ Sayed M, Pelech S, Wong C, Marotta A, Salh B. Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells. Oncogene. 2001 Oct 25;20(48):6994-7005. PMID:11704824 doi:10.1038/sj.onc.1204894
- ↑ Shin S, Lee Y, Kim W, Ko H, Choi H, Kim K. Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8. EMBO J. 2005 Oct 19;24(20):3532-42. Epub 2005 Sep 29. PMID:16193064 doi:10.1038/sj.emboj.7600827
- ↑ Tsuyuguchi M, Nakaniwa T, Hirasawa A, Nakanishi I, Kinoshita T. Structural insights for producing CK2alpha1-specific inhibitors. Bioorg Med Chem Lett. 2020 Jan 15;30(2):126837. doi: 10.1016/j.bmcl.2019.126837. , Epub 2019 Dec 3. PMID:31859160 doi:http://dx.doi.org/10.1016/j.bmcl.2019.126837
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