5mod - Revision history

OCA at 17:42, 8 November 2023

2023-11-08T17:42:01Z

← Older revision		Revision as of 17:42, 8 November 2023
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	<StructureSection load='5mod' size='340' side='right'caption='[[5mod]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='5mod' size='340' side='right'caption='[[5mod]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5mod]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5MOD FirstGlance]. <br>		<table><tr><td colspan='2'>[[5mod]] 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=5MOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MOD FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=86L:(3-CHLORANYL-4-PROPAN~~-2~~-YLOXY-PHENYL)METHANAMINE'>86L</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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]] 2.08Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=86L:(3-CHLORANYL-4-PROPAN-2-YLOXY-PHENYL)METHANAMINE'>86L</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5mod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mod OCA], [~~http~~://pdbe.org/5mod PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mod RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mod PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mod 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=5mod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mod OCA], [https://pdbe.org/5mod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mod RCSB], [https://www.ebi.ac.uk/pdbsum/5mod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mod ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>		[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific serine/threonine protein kinase]]~~		[[Category: Brear P]]
	[[Category: Brear, P]]		[[Category: De Fusco C]]
	[[Category: Fusco, C De]]		[[Category: Georgiou K]]
	[[Category: Georgiou, K]]		[[Category: Hyvonen M]]
	[[Category: Hyvonen, M]]		[[Category: Iegre J]]
	[[Category: Iegre, J]]		[[Category: Sore H]]
	[[Category: Sore, H]]		[[Category: Spring D]]
	[[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 at 07:24, 19 August 2020

2020-08-19T07:24:54Z

← Older revision		Revision as of 07:24, 19 August 2020
Line 1:		Line 1:

	==Crystal Structure of CK2alpha with N-(3-(((2-chloro-[1,1'-biphenyl]-4-yl)methyl)amino)propyl)methanesulfonamide bound==		==Crystal Structure of CK2alpha with N-(3-(((2-chloro-[1,1'-biphenyl]-4-yl)methyl)amino)propyl)methanesulfonamide bound==
	<StructureSection load='5mod' size='340' side='right' caption='[[5mod]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='5mod' size='340' side='right'caption='[[5mod]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5mod]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOD OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MOD FirstGlance]. <br>		<table><tr><td colspan='2'>[[5mod]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MOD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=86L:(3-CHLORANYL-4-PROPAN-2-YLOXY-PHENYL)METHANAMINE'>86L</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=86L:(3-CHLORANYL-4-PROPAN-2-YLOXY-PHENYL)METHANAMINE'>86L</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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='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=5mod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mod OCA], [http://pdbe.org/5mod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mod RCSB], [http://www.ebi.ac.uk/pdbsum/5mod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mod ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mod OCA], [http://pdbe.org/5mod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mod RCSB], [http://www.ebi.ac.uk/pdbsum/5mod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mod ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5mod" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mod" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Casein kinase 3D structures\|Casein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Brear, P]]		[[Category: Brear, P]]

OCA at 13:35, 24 May 2017

2017-05-24T13:35:44Z

← Older revision		Revision as of 13:35, 24 May 2017
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 5mod is ~~ON HOLD~~ ~~until Paper~~ Publication		==Crystal Structure of CK2alpha with N-(3-(((2-chloro-[1,1'-biphenyl]-4-yl)methyl)amino)propyl)methanesulfonamide bound==
			<StructureSection load='5mod' size='340' side='right' caption='[[5mod]], [[Resolution\|resolution]] 2.08Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5mod]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MOD FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=86L:(3-CHLORANYL-4-PROPAN-2-YLOXY-PHENYL)METHANAMINE'>86L</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=5mod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mod OCA], [http://pdbe.org/5mod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mod RCSB], [http://www.ebi.ac.uk/pdbsum/5mod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mod 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 ==
			Recently we reported the discovery of a potent and selective CK2alpha inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (alphaD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the alphaD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors.

	~~Authors: Brear, P~~., De Fusco, C., ~~Georgiou, K.~~, Iegre, J., Sore~~, H.~~, Hyvonen, M., Spring, D.		A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.,De Fusco C, Brear P, Iegre J, Georgiou KH, Sore HF, Hyvonen M, Spring DR Bioorg Med Chem. 2017 Apr 30. pii: S0968-0896(16)31479-1. doi:, 10.1016/j.bmc.2017.04.037. PMID:28495381<ref>PMID:28495381</ref>

	~~Description: Crystal Structure~~ of ~~CK2alpha with N~~-(3-~~(((2-chloro~~-[1,~~1'-biphenyl~~]~~-4-yl)methyl)amino)propyl)methanesulfonamide bound~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased Structures~~]]		</div>
			<div class="pdbe-citations 5mod" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Non-specific serine/threonine protein kinase]]
			[[Category: Brear, P]]
			[[Category: Fusco, C De]]
			[[Category: Georgiou, K]]
	[[Category: Hyvonen, M]]		[[Category: Hyvonen, M]]
	[[Category: ~~Georgiou~~, K]]		[[Category: Iegre, J]]
	[[Category: ~~Brear~~, P]]		[[Category: Sore, H]]
	[[Category: Spring, D]]		[[Category: Spring, D]]
	[[Category: ~~Sore, H~~]]		[[Category: Ck2a]]
	[[Category: ~~Iegre, J~~]]		[[Category: Ck2alpha]]
	[[Category: ~~De Fusco, C~~]]		[[Category: Fragment based drug discovery]]
			[[Category: High concentration screening]]
			[[Category: Selective atp competitive inhibitor]]
			[[Category: Surface entrophy reduction]]
			[[Category: Transferase]]

OCA at 11:29, 9 March 2017

2017-03-09T11:29:54Z

← Older revision		Revision as of 11:29, 9 March 2017
Line 9:		Line 9:
	[[Category: Hyvonen, M]]		[[Category: Hyvonen, M]]
	[[Category: Georgiou, K]]		[[Category: Georgiou, K]]
			[[Category: Brear, P]]
	[[Category: Spring, D]]		[[Category: Spring, D]]
			[[Category: Sore, H]]
	[[Category: Iegre, J]]		[[Category: Iegre, J]]
	[[Category: De Fusco, C]]		[[Category: De Fusco, C]]
	~~[[Category: Brear, P]]~~
	~~[[Category: Sore, H]]~~

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

2016-12-22T19:15:04Z

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

← Older revision	Revision as of 19:15, 22 December 2016
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5mod is ON HOLD until Paper Publication Authors: Brear, P., De Fusco, C., Georgiou, K., Iegre, J., Sore, H., Hyvonen, M., Spring, D. Description: C...

2016-12-22T19:15:03Z

New page: '''Unreleased structure''' The entry 5mod is ON HOLD until Paper Publication Authors: Brear, P., De Fusco, C., Georgiou, K., Iegre, J., Sore, H., Hyvonen, M., Spring, D. Description: C...

New page

'''Unreleased structure'''

The entry 5mod is ON HOLD until Paper Publication

Authors: Brear, P., De Fusco, C., Georgiou, K., Iegre, J., Sore, H., Hyvonen, M., Spring, D.

Description: Crystal Structure of CK2alpha with N-(3-(((2-chloro-[1,1'-biphenyl]-4-yl)methyl)amino)propyl)methanesulfonamide bound
[[Category: Unreleased Structures]]
[[Category: Hyvonen, M]]
[[Category: Georgiou, K]]
[[Category: Spring, D]]
[[Category: Iegre, J]]
[[Category: De Fusco, C]]
[[Category: Brear, P]]
[[Category: Sore, H]]