7zyr - Revision history

OCA at 13:35, 1 February 2024

2024-02-01T13:35:46Z

←Older revision		Revision as of 13:35, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7zyr]] is a 1 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=7ZYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZYR FirstGlance]. <br>		<table><tr><td colspan='2'>[[7zyr]] is a 1 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=7ZYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZYR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=KF6:5-bromanyl-6-chloranyl-3-(1~{H}-pyrrol-2-ylmethyl)-1~{H}-indole'>KF6</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]] 1.85Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=KF6:5-bromanyl-6-chloranyl-3-(1~{H}-pyrrol-2-ylmethyl)-1~{H}-indole'>KF6</scene></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=7zyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zyr OCA], [https://pdbe.org/7zyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zyr RCSB], [https://www.ebi.ac.uk/pdbsum/7zyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zyr ProSAT]</span></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=7zyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zyr OCA], [https://pdbe.org/7zyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zyr RCSB], [https://www.ebi.ac.uk/pdbsum/7zyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zyr ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:36, 7 December 2022

2022-12-07T08:36:35Z

←Older revision		Revision as of 08:36, 7 December 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7zyr is ~~ON HOLD until Paper~~ Publication	+	==Compound 20 Bound to CK2alpha==
		+	<StructureSection load='7zyr' size='340' side='right'caption='[[7zyr]], [[Resolution\|resolution]] 1.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7zyr]] is a 1 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=7ZYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZYR FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=KF6:5-bromanyl-6-chloranyl-3-(1~{H}-pyrrol-2-ylmethyl)-1~{H}-indole'>KF6</scene></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=7zyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zyr OCA], [https://pdbe.org/7zyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zyr RCSB], [https://www.ebi.ac.uk/pdbsum/7zyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zyr ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://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 ==
		+	CK2 is a ubiquitous protein kinase with an anti-apoptotic role and is found to be overexpressed in multiple cancer types. To this end, the inhibition of CK2 is of great interest with regard to the development of novel anti-cancer therapeutics. ATP-site inhibition of CK2 is possible; however, this typically results in poor selectivity due to the highly conserved nature of the catalytic site amongst kinases. An alternative methodology for the modulation of CK2 activity is through allosteric inhibition. The recently identified alphaD site represents a promising binding site for allosteric inhibition of CK2alpha. The work presented herein describes the development of a series of CK2alpha allosteric inhibitors through iterative cycles of X-ray crystallography and enzymatic assays, in addition to both fragment growing and fragment merging design strategies. The lead fragment developed, fragment 8, exhibits a high ligand efficiency, displays no drop off in activity between enzymatic and cellular assays, and successfully engages CK2alpha in cells. Furthermore, X-ray crystallographic analysis provided indications towards a novel mechanism of allosteric inhibition through alphaD site binding. Fragments described in this paper therefore represent promising starting points for the development of highly selective allosteric CK2 inhibitors.

-	~~Authors: Brear~~, P., ~~Hyvonen~~, M.	+	A fragment-based approach leading to the discovery of inhibitors of CK2alpha with a novel mechanism of action.,Brear P, De Fusco C, Atkinson EL, Iegre J, Francis-Newton NJ, Venkitaraman AR, Hyvonen M, Spring DR RSC Med Chem. 2022 Sep 16;13(11):1420-1426. doi: 10.1039/d2md00161f. eCollection , 2022 Nov 16. PMID:36426237<ref>PMID:36426237</ref>

-	~~Description~~: ~~Compound 20 Bound to CK2alpha~~	+	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 7zyr" style="background-color:#fffaf0;"></div>
-	[[Category: Brear, P]]	+
		+	==See Also==
		+	*[[Casein kinase 3D structures\|Casein kinase 3D structures]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Brear P]]
		+	[[Category: Hyvonen M]]

OCA at 06:18, 29 June 2022

2022-06-29T06:18:08Z

←Older revision		Revision as of 06:18, 29 June 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7zyr is ON HOLD	+	The entry 7zyr is ON HOLD until Paper Publication

	Authors: Brear, P., Hyvonen, M.		Authors: Brear, P., Hyvonen, M.

OCA: Protected "7zyr" [edit=sysop:move=sysop]

2022-06-08T04:18:25Z

Protected "7zyr" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:18, 8 June 2022

OCA: New page: '''Unreleased structure''' The entry 7zyr is ON HOLD Authors: Brear, P., Hyvonen, M. Description: Compound 20 Bound to CK2alpha Category: Unreleased Structures [[Category: Hyvonen,...

2022-06-08T04:18:24Z

New page: '''Unreleased structure''' The entry 7zyr is ON HOLD Authors: Brear, P., Hyvonen, M. Description: Compound 20 Bound to CK2alpha Category: Unreleased Structures [[Category: Hyvonen,...

New page

'''Unreleased structure'''

The entry 7zyr is ON HOLD

Authors: Brear, P., Hyvonen, M.

Description: Compound 20 Bound to CK2alpha
[[Category: Unreleased Structures]]
[[Category: Hyvonen, M]]
[[Category: Brear, P]]