This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4kwp

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 10:15, 4 August 2016

Crystal Structure of Human CK2-alpha in complex with a benzimidazole inhibitor (K164) at 1.25 A resolution

Structural highlights

4kwp is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Gene:	CSNK2A1, CK2A1 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

It has been proposed that dual inhibitors of protein kinases CK2 and PIM-1 are tools particularly valuable to induce apoptosis of cancer cells, a property, however, implying cell permeability, which is lacking in the case of selective CK2/PIM-1 inhibitors developed so far. To fill this gap, we have derivatized the scaffold of the promiscuous CK2 inhibitor TBI with a deoxyribose moiety, generating TDB, a selective, cell-permeable inhibitor of CK2 and PIM-1. Here, we shed light on the structural features underlying the potency and narrow selectivity of TDB by exploiting a number of TDB analogs and by solving the 3D structure of the TDB/CK2 complex at 1.25 A resolution, one of the highest reported so far for this kinase. We also show that the cytotoxic efficacy of TDB is almost entirely due to apoptosis, is accompanied by parallel inhibition of cellular CK2 and PIM-1, and is superior to both those observed combining individual inhibitors of CK2 and PIM-1 and by treating cells with the CK2 inhibitor CX4945. These data, in conjunction with the observations that cancer cells are more susceptible than non-cancer cells to TDB and that such a sensitivity is maintained in a multi-drug resistance background, highlight the pharmacological potential of this compound.

Cell-permeable dual inhibitors of protein kinases CK2 and PIM-1: structural features and pharmacological potential.,Cozza G, Girardi C, Ranchio A, Lolli G, Sarno S, Orzeszko A, Kazimierczuk Z, Battistutta R, Ruzzene M, Pinna LA Cell Mol Life Sci. 2014 Jan 18. PMID:24442476^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ St-Denis NA, Derksen DR, Litchfield DW. Evidence for regulation of mitotic progression through temporal phosphorylation and dephosphorylation of CK2alpha. Mol Cell Biol. 2009 Apr;29(8):2068-81. doi: 10.1128/MCB.01563-08. Epub 2009 Feb, 2. PMID:19188443 doi:10.1128/MCB.01563-08
↑ Cozza G, Girardi C, Ranchio A, Lolli G, Sarno S, Orzeszko A, Kazimierczuk Z, Battistutta R, Ruzzene M, Pinna LA. Cell-permeable dual inhibitors of protein kinases CK2 and PIM-1: structural features and pharmacological potential. Cell Mol Life Sci. 2014 Jan 18. PMID:24442476 doi:http://dx.doi.org/10.1007/s00018-013-1552-5

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kwp"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human CK2-alpha in complex with a benzimidazole inhibitor (K164) at 1.25 A resolution==
 <StructureSection load='4kwp' size='340' side='right' caption='[[4kwp]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSNK2A1, CK2A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=4kwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kwp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kwp RCSB], [http://www.ebi.ac.uk/pdbsum/4kwp PDBsum]</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=4kwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kwp OCA], [http://pdbe.org/4kwp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kwp RCSB], [http://www.ebi.ac.uk/pdbsum/4kwp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kwp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4kwp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Casein kinase|Casein kinase]]
 == References ==
 <references/>

4kwp

From Proteopedia

Revision as of 10:15, 4 August 2016

Crystal Structure of Human CK2-alpha in complex with a benzimidazole inhibitor (K164) at 1.25 A resolution

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox