5m4c

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'''Unreleased structure'''
 
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The entry 5m4c is ON HOLD until Paper Publication
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==Complex structure of human protein kinase CK2 catalytic subunit with a thieno[2,3-d]pyrimidin inhibitor crystallized under low-salt conditions==
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<StructureSection load='5m4c' size='340' side='right' caption='[[5m4c]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5m4c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M4C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M4C FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7EY:3-[5-(4-METHYLPHENYL)THIENO[2,3-D]PYRIMIDIN-4-YL]SULFANYLPROPANOIC+ACID'>7EY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5m44|5m44]]</td></tr>
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<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>
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<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=5m4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m4c OCA], [http://pdbe.org/5m4c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m4c RCSB], [http://www.ebi.ac.uk/pdbsum/5m4c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m4c ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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CK2 is a Ser/Thr kinase recruited by tumor cells to avoid cell death. 4'-Carboxy-6,8-dibromo-flavonol (FLC26) is a nanomolar CK2 inhibitor reducing the physiological phosphorylation of CK2 biomarkers and inducing cell death. Its binding mode to the ATP site was predicted to depend primarily on noncovalent interactions not comprising halogen bonds. We confirm this by two independent cocrystal structures which additionally show that FLC26 is selective for an open, protein kinase-untypical conformation of the hinge/helix alphaD region. The structures suggest how the bromo substituents, found previously in lead optimization studies, contribute to the inhibitory efficacy. In this context, one of the complex structures, obtained by crystallization with the kosmotropic salt NaCl, revealed an unconventional pi-halogen bond between the 8-bromo substituent of FLC26 and an aromatic side chain which is absent under low-salt conditions. The kosmotropic salt sensitivity of pi-halogen bonds is a novel feature which requires attention in structural comparisons and halogen-bond-based explanations.
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Authors: Niefind, K., Bischoff, N., Yarmoluk, S.M., Bdzhola, V.G., Golub, A.G., Balanda, A.O., Prykhod'ko, A.O.
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A Note of Caution on the Role of Halogen Bonds for Protein Kinase/Inhibitor Recognition Suggested by High- And Low-Salt CK2alpha Complex Structures.,Guerra B, Bischoff N, Bdzhola VG, Yarmoluk SM, Issinger OG, Golub AG, Niefind K ACS Chem Biol. 2015 May 15. PMID:25961323<ref>PMID:25961323</ref>
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Description: Complex structure of human protein kinase CK2 catalytic subunit with a thieno[2,3-d]pyrimidin inhibitor crystallized under low-salt conditions
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Golub, A.G]]
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<div class="pdbe-citations 5m4c" style="background-color:#fffaf0;"></div>
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[[Category: Balanda, A.O]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Balanda, A O]]
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[[Category: Bdzhola, V G]]
[[Category: Bischoff, N]]
[[Category: Bischoff, N]]
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[[Category: Yarmoluk, S.M]]
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[[Category: Golub, A G]]
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[[Category: Bdzhola, V.G]]
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[[Category: Niefind, K]]
[[Category: Niefind, K]]
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[[Category: Prykhod'Ko, A.O]]
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[[Category: Yarmoluk, S M]]
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[[Category: Ko, A O.Prykhod]]
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[[Category: Casein kinase 2]]
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[[Category: Protein kinase ck2]]
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[[Category: Transferase]]

Revision as of 16:12, 18 January 2017

Complex structure of human protein kinase CK2 catalytic subunit with a thieno[2,3-d]pyrimidin inhibitor crystallized under low-salt conditions

5m4c, resolution 1.94Å

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