5m56 - Revision history

OCA at 18:26, 1 November 2023

2023-11-01T18:26:21Z

←Older revision		Revision as of 18:26, 1 November 2023
Line 1:		Line 1:

	==Monoclinic complex structure of human protein kinase CK2 catalytic subunit (isoform CK2alpha') with the inhibitor 4'-carboxy-6,8-chloro-flavonol (FLC21)==		==Monoclinic complex structure of human protein kinase CK2 catalytic subunit (isoform CK2alpha') with the inhibitor 4'-carboxy-6,8-chloro-flavonol (FLC21)==
-	<StructureSection load='5m56' size='340' side='right' caption='[[5m56]], [[Resolution\|resolution]] 2.24Å' scene=''>	+	<StructureSection load='5m56' size='340' side='right'caption='[[5m56]], [[Resolution\|resolution]] 2.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5m56]] 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=5M56 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5M56 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5m56]] is a 2 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=5M56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M56 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FC:4-[6,8-BIS(CHLORANYL)-3-OXIDANYL-4-OXIDANYLIDENE-CHROMEN-2-YL]BENZOIC+ACID'>7FC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.237Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m4u\|5m4u]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7FC:4-[6,8-BIS(CHLORANYL)-3-OXIDANYL-4-OXIDANYLIDENE-CHROMEN-2-YL]BENZOIC+ACID'>7FC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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 HUMAN])</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=5m56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m56 OCA], [https://pdbe.org/5m56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m56 RCSB], [https://www.ebi.ac.uk/pdbsum/5m56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m56 ProSAT]</span></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=5m56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m56 OCA], [~~http~~://pdbe.org/5m56 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5m56 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5m56 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5m56 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 ==
Line 23:		Line 21:

	==See Also==		==See Also==
-	*[[Casein kinase\|Casein kinase]]	+	*[[Casein kinase 3D structures\|Casein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Balanda~~, A O~~]]	+	[[Category: Balanda AO]]
-	[[Category: Bdzhola~~, V G~~]]	+	[[Category: Bdzhola VG]]
-	[[Category: Bischoff, N]]	+	[[Category: Bischoff N]]
-	[[Category: Golub~~, A G~~]]	+	[[Category: Golub AG]]
-	[[Category: Niefind, K]]	+	[[Category: Niefind K]]
-	[[Category: ~~Yarmoluk, S M]]~~	+	[[Category: Prykhod'ko AO]]
-	~~[[Category: Ko, A O.~~Prykhod]]	+	[[Category: Yarmoluk SM]]
-	[[Category: ~~Casein kinase 2]]~~	+
-	~~[[Category: Protein kinase ck2]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:22, 10 October 2018

2018-10-10T08:22:49Z

←Older revision		Revision as of 08:22, 10 October 2018
Line 3:		Line 3:
	<StructureSection load='5m56' size='340' side='right' caption='[[5m56]], [[Resolution\|resolution]] 2.24Å' scene=''>		<StructureSection load='5m56' size='340' side='right' caption='[[5m56]], [[Resolution\|resolution]] 2.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5m56]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M56 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5m56]] 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=5M56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M56 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FC:4-[6,8-BIS(CHLORANYL)-3-OXIDANYL-4-OXIDANYLIDENE-CHROMEN-2-YL]BENZOIC+ACID'>7FC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FC:4-[6,8-BIS(CHLORANYL)-3-OXIDANYL-4-OXIDANYLIDENE-CHROMEN-2-YL]BENZOIC+ACID'>7FC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m4u\|5m4u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m4u\|5m4u]]</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='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=5m56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m56 OCA], [http://pdbe.org/5m56 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m56 RCSB], [http://www.ebi.ac.uk/pdbsum/5m56 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m56 ProSAT]</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=5m56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m56 OCA], [http://pdbe.org/5m56 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m56 RCSB], [http://www.ebi.ac.uk/pdbsum/5m56 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m56 ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Balanda, A O]]		[[Category: Balanda, A O]]

OCA at 06:25, 10 May 2017

2017-05-10T06:25:47Z

←Older revision		Revision as of 06:25, 10 May 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5m56" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5m56" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Casein kinase\|Casein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:36, 25 January 2017

2017-01-25T16:36:53Z

←Older revision		Revision as of 16:36, 25 January 2017
Line 13:		Line 13:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	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~~.	+	Protein kinase CK2 is associated with a number of human diseases, among them cancer, and is therefore a target for inhibitor development in industry and academia. Six crystal structures of either CK2alpha, the catalytic subunit of human protein kinase CK2, or its paralog CK2alpha' in complex with two ATP-competitive inhibitors-based on either a flavonol or a thieno[2,3-d]pyrimidine framework-are presented. The structures show examples for extreme structural deformations of the ATP-binding loop and its neighbourhood and of the hinge/helix alphaD region, i.e., of two zones of the broader ATP site environment. Thus, they supplement our picture of the conformational space available for CK2alpha and CK2alpha'. Further, they document the potential of synthetic ligands to trap unusual conformations of the enzymes and allow to envision a new generation of inhibitors that stabilize such conformations.

-	~~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>	+	Structural Hypervariability of the Two Human Protein Kinase CK2 Catalytic Subunit Paralogs Revealed by Complex Structures with a Flavonol- and a Thieno[2,3-d]pyrimidine-Based Inhibitor.,Niefind K, Bischoff N, Golub AG, Bdzhola VG, Balanda AO, Prykhod'ko AO, Yarmoluk SM Pharmaceuticals (Basel). 2017 Jan 11;10(1). pii: E9. doi: 10.3390/ph10010009. PMID:28085026<ref>PMID:28085026</ref>

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

OCA at 16:14, 18 January 2017

2017-01-18T16:14:26Z

←Older revision		Revision as of 16:14, 18 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5m56 is ~~ON HOLD~~	+	==Monoclinic complex structure of human protein kinase CK2 catalytic subunit (isoform CK2alpha') with the inhibitor 4'-carboxy-6,8-chloro-flavonol (FLC21)==
		+	<StructureSection load='5m56' size='340' side='right' caption='[[5m56]], [[Resolution\|resolution]] 2.24Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5m56]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M56 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7FC:4-[6,8-BIS(CHLORANYL)-3-OXIDANYL-4-OXIDANYLIDENE-CHROMEN-2-YL]BENZOIC+ACID'>7FC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m4u\|5m4u]]</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=5m56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m56 OCA], [http://pdbe.org/5m56 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m56 RCSB], [http://www.ebi.ac.uk/pdbsum/5m56 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m56 ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	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.

-	~~Authors: Niefind, K~~., Bischoff, N., Yarmoluk, ~~S.M., Bdzhola, V.G.~~, Golub, A.~~G., Balanda, A.O., Prykhod'ko, A.O~~.	+	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>

-	~~Description: Monoclinic complex structure~~ of ~~human protein kinase CK2 catalytic subunit (isoform CK2alpha') with~~ the ~~inhibitor 4'-carboxy-6,8~~-~~chloro~~-~~flavonol (FLC21)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Golub~~, A.G]]	+	<div class="pdbe-citations 5m56" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Balanda~~, ~~A.O~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Balanda, A O]]
		+	[[Category: Bdzhola, V G]]
	[[Category: Bischoff, N]]		[[Category: Bischoff, N]]
-	[[Category: ~~Yarmoluk~~, ~~S.M]]~~	+	[[Category: Golub, A G]]
-	~~[[Category: Bdzhola, V.~~G]]	+
	[[Category: Niefind, K]]		[[Category: Niefind, K]]
-	[[Category: ~~Prykhod'~~Ko, A.O]]	+	[[Category: Yarmoluk, S M]]
		+	[[Category: Ko, A O.Prykhod]]
		+	[[Category: Casein kinase 2]]
		+	[[Category: Protein kinase ck2]]
		+	[[Category: Transferase]]

OCA: Protected "5m56" [edit=sysop:move=sysop]

2016-10-26T16:25:54Z

Protected "5m56" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:25, 26 October 2016

OCA: New page: '''Unreleased structure''' The entry 5m56 is ON HOLD Authors: Niefind, K., Bischoff, N., Yarmoluk, S.M., Bdzhola, V.G., Golub, A.G., Balanda, A.O., Prykhod'ko, A.O. Description: Monocl...

2016-10-26T16:25:53Z

New page: '''Unreleased structure''' The entry 5m56 is ON HOLD Authors: Niefind, K., Bischoff, N., Yarmoluk, S.M., Bdzhola, V.G., Golub, A.G., Balanda, A.O., Prykhod'ko, A.O. Description: Monocl...

New page

'''Unreleased structure'''

The entry 5m56 is ON HOLD

Authors: Niefind, K., Bischoff, N., Yarmoluk, S.M., Bdzhola, V.G., Golub, A.G., Balanda, A.O., Prykhod'ko, A.O.

Description: Monoclinic complex structure of human protein kinase CK2 catalytic subunit (isoform CK2alpha') with the inhibitor 4'-carboxy-6,8-chloro-flavonol (FLC21)
[[Category: Unreleased Structures]]
[[Category: Golub, A.G]]
[[Category: Balanda, A.O]]
[[Category: Bischoff, N]]
[[Category: Yarmoluk, S.M]]
[[Category: Bdzhola, V.G]]
[[Category: Niefind, K]]
[[Category: Prykhod'Ko, A.O]]