3w8l

From Proteopedia

(Difference between revisions)

Revision as of 05:56, 14 October 2020

Crystal structure of human CK2 in complex with inositol hexakisphosphate

Structural highlights

3w8l is a 2 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

Protein kinase CK2 is a ubiquitous kinase that can phosphorylate hundreds of cellular proteins and plays important roles in cell growth and development. Deregulation of CK2 is related to a variety of human cancers, and CK2 is regarded as a suppressor of apoptosis; therefore, it is a target of anticancer therapy. Nucleolar phosphoprotein 140 (Nopp140), which is an intrinsically disordered protein, interacts with CK2 and inhibits the latter's catalytic activity in vitro. Interestingly, the catalytic activity of CK2 is recovered in the presence of d-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP6). IP6 is widely distributed in animal cells, but the molecular mechanisms that govern its cellular functions in animal cells have not been completely elucidated. In this study, the crystal structure of CK2 in complex with IP6 showed that the lysine-rich cluster of CK2 plays an important role in binding to IP6. The biochemical experiments revealed that a Nopp140 fragment (residues 568-596) and IP6 competitively bind to the catalytic subunit of CK2 (CK2alpha), and phospho-Ser574 of Nopp140 significantly enhances its interaction with CK2alpha. Substitutions of K74E, K76E, and K77E in CK2alpha significantly reduced the interactions of CK2alpha with both IP6 and the Nopp140-derived peptide. Our study gives an insight into the regulation of CK2. In particular, our work suggests that CK2 activity is inhibited by Nopp140 and reactivated by IP6 by competitive binding at the substrate recognition site of CK2.

Structural and functional insights into the regulation mechanism of CK2 by IP6 and the intrinsically disordered protein Nopp140.,Lee WK, Son SH, Jin BS, Na JH, Kim SY, Kim KH, Kim EE, Yu YG, Lee HH Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19360-5. doi:, 10.1073/pnas.1304670110. Epub 2013 Nov 11. PMID:24218616^[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
↑ Lee WK, Son SH, Jin BS, Na JH, Kim SY, Kim KH, Kim EE, Yu YG, Lee HH. Structural and functional insights into the regulation mechanism of CK2 by IP6 and the intrinsically disordered protein Nopp140. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19360-5. doi:, 10.1073/pnas.1304670110. Epub 2013 Nov 11. PMID:24218616 doi:http://dx.doi.org/10.1073/pnas.1304670110

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/3w8l"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human CK2 in complex with inositol hexakisphosphate==
-<StructureSection load='3w8l' size='340' side='right' caption='[[3w8l]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='3w8l' size='340' side='right'caption='[[3w8l]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3w8l]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W8L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W8L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3w8l]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W8L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3W8L FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I6P:INOSITOL+1,2,3,4,5,6-HEXAKISPHOSPHATE'>I6P</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene></td></tr>
 <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=3w8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w8l OCA], [http://pdbe.org/3w8l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w8l RCSB], [http://www.ebi.ac.uk/pdbsum/3w8l PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3w8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w8l OCA], [http://pdbe.org/3w8l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w8l RCSB], [http://www.ebi.ac.uk/pdbsum/3w8l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3w8l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 ==See Also==
-*[[Casein kinase|Casein kinase]]
+*[[Casein kinase 3D structures|Casein kinase 3D structures]]
 == References ==
 <references/>
@@ Line 27: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Lee, H H]]

3w8l

From Proteopedia

Revision as of 05:56, 14 October 2020

Crystal structure of human CK2 in complex with inositol hexakisphosphate

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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