5m57 - Revision history

OCA at 18:26, 1 November 2023

OCA — Wed, 01 Nov 2023 18:26:22 GMT

←Older revision		Revision as of 18:26, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='5m57' size='340' side='right'caption='[[5m57]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='5m57' size='340' side='right'caption='[[5m57]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5m57]] 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=5M57 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5M57 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5m57]] 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=5M57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M57 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=4SP:O6-CYCLOHEXYLMETHOXY~~-2~~-(4-SULPHAMOYLANILINO)+PURINE'>4SP</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]] 2.3Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>NEK2, NEK2A, NLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4SP:O6-CYCLOHEXYLMETHOXY-2-(4-SULPHAMOYLANILINO)+PURINE'>4SP</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'>[https://proteopedia.org/fgij/fg.htm?mol=5m57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m57 OCA], [https://pdbe.org/5m57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m57 RCSB], [https://www.ebi.ac.uk/pdbsum/5m57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m57 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=5m57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m57 OCA], [~~http~~://pdbe.org/5m57 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5m57 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5m57 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5m57 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NEK2_HUMAN NEK2_HUMAN]] Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not.<ref>PMID:11742531</ref> <ref>PMID:14978040</ref> <ref>PMID:12857871</ref> <ref>PMID:15358203</ref> <ref>PMID:15388344</ref> <ref>PMID:15161910</ref> <ref>PMID:17283141</ref> <ref>PMID:17621308</ref> <ref>PMID:17626005</ref> <ref>PMID:18086858</ref> <ref>PMID:18297113</ref> <ref>PMID:20034488</ref> <ref>PMID:21076410</ref>	+	[https://www.uniprot.org/uniprot/NEK2_HUMAN NEK2_HUMAN] Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not.<ref>PMID:11742531</ref> <ref>PMID:14978040</ref> <ref>PMID:12857871</ref> <ref>PMID:15358203</ref> <ref>PMID:15388344</ref> <ref>PMID:15161910</ref> <ref>PMID:17283141</ref> <ref>PMID:17621308</ref> <ref>PMID:17626005</ref> <ref>PMID:18086858</ref> <ref>PMID:18297113</ref> <ref>PMID:20034488</ref> <ref>PMID:21076410</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Bayliss R]]
-	[[Category: Bayliss, R]]	+
-	~~[[Category: Centrosome separation]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 11:01, 12 August 2020

OCA — Wed, 12 Aug 2020 11:01:47 GMT

←Older revision		Revision as of 11:01, 12 August 2020
Line 1:		Line 1:

	==Nek2 bound to arylaminopurine 6==		==Nek2 bound to arylaminopurine 6==
-	<StructureSection load='5m57' size='340' side='right' caption='[[5m57]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='5m57' size='340' side='right'caption='[[5m57]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5m57]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M57 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5M57 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5m57]] 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=5M57 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5M57 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4SP:O6-CYCLOHEXYLMETHOXY-2-(4-SULPHAMOYLANILINO)+PURINE'>4SP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4SP:O6-CYCLOHEXYLMETHOXY-2-(4-SULPHAMOYLANILINO)+PURINE'>4SP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NEK2, NEK2A, NLK1 ([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=5m57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m57 OCA], [http://pdbe.org/5m57 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m57 RCSB], [http://www.ebi.ac.uk/pdbsum/5m57 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m57 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=5m57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m57 OCA], [http://pdbe.org/5m57 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m57 RCSB], [http://www.ebi.ac.uk/pdbsum/5m57 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m57 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5m57" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5m57" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bayliss, R]]		[[Category: Bayliss, R]]

OCA at 10:57, 10 December 2016

OCA — Sat, 10 Dec 2016 10:57:07 GMT

←Older revision		Revision as of 10:57, 10 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5m57 is ~~ON HOLD~~	+	==Nek2 bound to arylaminopurine 6==
		+	<StructureSection load='5m57' size='340' side='right' caption='[[5m57]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5m57]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M57 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M57 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4SP:O6-CYCLOHEXYLMETHOXY-2-(4-SULPHAMOYLANILINO)+PURINE'>4SP</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=5m57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m57 OCA], [http://pdbe.org/5m57 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m57 RCSB], [http://www.ebi.ac.uk/pdbsum/5m57 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m57 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NEK2_HUMAN NEK2_HUMAN]] Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not.<ref>PMID:11742531</ref> <ref>PMID:14978040</ref> <ref>PMID:12857871</ref> <ref>PMID:15358203</ref> <ref>PMID:15388344</ref> <ref>PMID:15161910</ref> <ref>PMID:17283141</ref> <ref>PMID:17621308</ref> <ref>PMID:17626005</ref> <ref>PMID:18086858</ref> <ref>PMID:18297113</ref> <ref>PMID:20034488</ref> <ref>PMID:21076410</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can restrict tumor cell growth and promote apoptosis. Nek2 inhibition with small molecules, therefore, offers the prospect of a new therapy for cancer. To achieve this goal, a better understanding of the requirements for selective-inhibition of Nek2 is required. 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. Comparison with CDK2-inhibitor structures indicated that judicious modification of the 6-alkoxy and 2-arylamino substituents could achieve discrimination between Nek2 and CDK2. In this study, a library of 6-cyclohexylmethoxy-2-arylaminopurines bearing carboxamide, sulfonamide and urea substituents on the 2-arylamino ring was synthesized. Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for 3-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)-N,N-dimethylbenzamide (CDK2 IC50 = 7.0 muM; Nek2 IC50 = 0.62 muM) with >10-fold selectivity. Deletion of the 6-substituent abrogated activity against both Nek2 and CDK2. Nine compounds containing an (E)-dialkylaminovinyl substituent at C-6, all showed selectivity for Nek2, e.g. (E)-6-(2-(azepan-1-yl)vinyl)-N-phenyl-9H-purin-2-amine (CDK2 IC50 = 2.70 muM; Nek2 IC50 = 0.27 muM). Structural biology of selected compounds enabled a partial rationalization of the observed structure activity relationships and mechanism of Nek2 activation. This showed that carboxamide 11 is the first reported inhibitor of Nek2 in the DFG-in conformation.

-	~~Authors: Bayliss~~, R.	+	Structure-guided design of purine-based probes for selective Nek2 inhibition.,Coxon CR, Wong C, Bayliss R, Boxall K, Carr KH, Fry AM, Hardcastle IR, Matheson CJ, Newell DR, Sivaprakasam M, Thomas H, Turner D, Yeoh S, Wang LZ, Griffin RJ, Golding BT, Cano C Oncotarget. 2016 Nov 9. doi: 10.18632/oncotarget.13249. PMID:27833088<ref>PMID:27833088</ref>

-	~~Description~~: ~~Nek2 bound to arylaminopurine 6~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5m57" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Bayliss, R]]		[[Category: Bayliss, R]]
		+	[[Category: Centrosome separation]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

OCA: Protected "5m57" [edit=sysop:move=sysop]

OCA — Wed, 26 Oct 2016 16:25:58 GMT

Protected "5m57" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:25, 26 October 2016

OCA: New page: '''Unreleased structure''' The entry 5m57 is ON HOLD Authors: Bayliss, R. Description: Nek2 bound to arylaminopurine 6 Category: Unreleased Structures Category: Bayliss, R

OCA — Wed, 26 Oct 2016 16:25:56 GMT

New page: '''Unreleased structure''' The entry 5m57 is ON HOLD Authors: Bayliss, R. Description: Nek2 bound to arylaminopurine 6 Category: Unreleased Structures Category: Bayliss, R

New page

'''Unreleased structure'''

The entry 5m57 is ON HOLD

Authors: Bayliss, R.

Description: Nek2 bound to arylaminopurine 6
[[Category: Unreleased Structures]]
[[Category: Bayliss, R]]