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.

3e3b

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 00:29, 5 August 2016

Crystal structure of catalytic subunit of human protein kinase CK2alpha prime with a potent indazole-derivative inhibitor

Structural highlights

3e3b 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:	CSNK2A2, CK2A2 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2alpha1 or CK2alpha2) and two regulatory subunits (CK2beta). The two isozymes CK2alpha1 and CK2alpha2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2alpha1-selective inhibitors, the crystal structure of human CK2alpha2 (hCK2alpha2) complexed with a potent CK2alpha inhibitor which binds to the active site of hCK2alpha2 was determined and compared with that of human CK2alpha1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the beta4-beta5 loop responsible for the CK2alpha-CK2beta interface. The top of the N-terminal segment interacted with the beta4-beta5 loop via a hydrogen bond in hCK2alpha2 but not in hCK2alpha1. Thus, the CK2alpha-CK2beta interface is a likely target candidate for the production of selective CK2alpha1 inhibitors.

Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor.,Nakaniwa T, Kinoshita T, Sekiguchi Y, Tada T, Nakanishi I, Kitaura K, Suzuki Y, Ohno H, Hirasawa A, Tsujimoto G Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Feb 1;65(Pt, 2):75-9. Epub 2009 Jan 31. PMID:19193990^[4]

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
↑ Nakaniwa T, Kinoshita T, Sekiguchi Y, Tada T, Nakanishi I, Kitaura K, Suzuki Y, Ohno H, Hirasawa A, Tsujimoto G. Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Feb 1;65(Pt, 2):75-9. Epub 2009 Jan 31. PMID:19193990 doi:10.1107/S1744309108043194

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3e3b"

@@ Line 1: / Line 1: @@
 ==Crystal structure of catalytic subunit of human protein kinase CK2alpha prime with a potent indazole-derivative inhibitor==
 <StructureSection load='3e3b' size='340' side='right' caption='[[3e3b]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3e3b]] 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=3E3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E3B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3e3b]] is a 1 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=3E3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E3B FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CCK:[1-(6-{6-[(1-METHYLETHYL)AMINO]-1H-INDAZOL-1-YL}PYRAZIN-2-YL)-1H-PYRROL-3-YL]ACETIC+ACID'>CCK</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSNK2A2, CK2A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSNK2A2, CK2A2 ([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=3e3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e3b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e3b RCSB], [http://www.ebi.ac.uk/pdbsum/3e3b 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=3e3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e3b OCA], [http://pdbe.org/3e3b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e3b RCSB], [http://www.ebi.ac.uk/pdbsum/3e3b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3e3b ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3e3b ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3e3b" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Kinoshita, T]]

3e3b

From Proteopedia

Revision as of 00:29, 5 August 2016

Crystal structure of catalytic subunit of human protein kinase CK2alpha prime with a potent indazole-derivative inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox