6gih - Revision history

OCA at 06:35, 20 June 2018

2018-06-20T06:35:20Z

←Older revision		Revision as of 06:35, 20 June 2018
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	<StructureSection load='6gih' size='340' side='right' caption='[[6gih]], [[Resolution\|resolution]] 1.96Å' scene=''>		<StructureSection load='6gih' size='340' side='right' caption='[[6gih]], [[Resolution\|resolution]] 1.96Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gih]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gih]] 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=6GIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EZN:[3-chloranyl-5-(1~{H}-indol-4-yl)phenyl]methanamine'>EZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EZN:[3-chloranyl-5-(1~{H}-indol-4-yl)phenyl]methanamine'>EZN</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='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=6gih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gih OCA], [http://pdbe.org/6gih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gih RCSB], [http://www.ebi.ac.uk/pdbsum/6gih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gih 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=6gih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gih OCA], [http://pdbe.org/6gih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gih RCSB], [http://www.ebi.ac.uk/pdbsum/6gih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gih ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Brear, P]]		[[Category: Brear, P]]

OCA at 07:30, 23 May 2018

2018-05-23T07:30:50Z

←Older revision		Revision as of 07:30, 23 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6gih is ~~ON HOLD~~	+	==Crystal Structure of CK2alpha with CAM187 bound==
		+	<StructureSection load='6gih' size='340' side='right' caption='[[6gih]], [[Resolution\|resolution]] 1.96Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6gih]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIH FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EZN:[3-chloranyl-5-(1~{H}-indol-4-yl)phenyl]methanamine'>EZN</scene></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=6gih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gih OCA], [http://pdbe.org/6gih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gih RCSB], [http://www.ebi.ac.uk/pdbsum/6gih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gih ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2alpha and CK2beta at the alpha-beta interface of the holoenzyme. A fragment, CAM187, with an IC50 of 44muM and a molecular weight of only 257gmol(-1) has been identified as the most promising compound. Importantly, the lead fragment only bound at the interface and was not observed in the ATP binding site of the protein when co-crystallised with CK2alpha. The fragment-like molecules discovered in this study represent unique scaffolds to CK2 inhibition and leave room for further optimisation.

-	~~Authors:~~ Brear, P~~., Iegre, J.~~, North, A., ~~De Fusco, C.~~, Georgiou, K., Lubin, A., Carro, L., Sore~~, H.~~, Hyvonen, M., Spring, D.	+	Novel non-ATP competitive small molecules targeting the CK2 alpha/beta interface.,Brear P, North A, Iegre J, Hadje Georgiou K, Lubin A, Carro L, Green W, Sore HF, Hyvonen M, Spring DR Bioorg Med Chem. 2018 May 9. pii: S0968-0896(18)30329-8. doi:, 10.1016/j.bmc.2018.05.011. PMID:29759799<ref>PMID:29759799</ref>

-	~~Description: Crystal Structure~~ of ~~CK2alpha with CAM187 bound~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Hyvonen~~, M]]	+	<div class="pdbe-citations 6gih" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Brear, P]]
		+	[[Category: Carro, L]]
		+	[[Category: Fusco, C De]]
	[[Category: Georgiou, K]]		[[Category: Georgiou, K]]
-	[[Category: ~~Lubin~~, ~~A]]~~	+	[[Category: Hyvonen, M]]
-	~~[[Category: Spring, D~~]]	+
	[[Category: Iegre, J]]		[[Category: Iegre, J]]
-	[[Category: ~~De Fusco~~, C]]	+	[[Category: Lubin, A]]
	[[Category: North, A]]		[[Category: North, A]]
-	[[Category: Brear, P]]
	[[Category: Sore, H]]		[[Category: Sore, H]]
-	[[Category: ~~Carro~~, L]]	+	[[Category: Spring, D]]
		+	[[Category: Ck2a]]
		+	[[Category: Ck2alpha]]
		+	[[Category: Fragment based drug discovery]]
		+	[[Category: High concentration screening]]
		+	[[Category: Selective atp competitive inhibitor]]
		+	[[Category: Surface entrophy reduction]]
		+	[[Category: Transferase]]

OCA: Protected "6gih" [edit=sysop:move=sysop]

2018-05-16T04:17:21Z

Protected "6gih" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:17, 16 May 2018

OCA: New page: '''Unreleased structure''' The entry 6gih is ON HOLD Authors: Brear, P., Iegre, J., North, A., De Fusco, C., Georgiou, K., Lubin, A., Carro, L., Sore, H., Hyvonen, M., Spring, D. Descr...

2018-05-16T04:17:20Z

New page: '''Unreleased structure''' The entry 6gih is ON HOLD Authors: Brear, P., Iegre, J., North, A., De Fusco, C., Georgiou, K., Lubin, A., Carro, L., Sore, H., Hyvonen, M., Spring, D. Descr...

New page

'''Unreleased structure'''

The entry 6gih is ON HOLD

Authors: Brear, P., Iegre, J., North, A., De Fusco, C., Georgiou, K., Lubin, A., Carro, L., Sore, H., Hyvonen, M., Spring, D.

Description: Crystal Structure of CK2alpha with CAM187 bound
[[Category: Unreleased Structures]]
[[Category: Hyvonen, M]]
[[Category: Georgiou, K]]
[[Category: Lubin, A]]
[[Category: Spring, D]]
[[Category: Iegre, J]]
[[Category: De Fusco, C]]
[[Category: North, A]]
[[Category: Brear, P]]
[[Category: Sore, H]]
[[Category: Carro, L]]