5cyi - Revision history

OCA at 11:23, 10 January 2024

2024-01-10T11:23:37Z

←Older revision		Revision as of 11:23, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5cyi]] is a 4 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=5CYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CYI FirstGlance]. <br>		<table><tr><td colspan='2'>[[5cyi]] is a 4 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=5CYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CYI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [https://pdbe.org/5cyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [https://www.ebi.ac.uk/pdbsum/5cyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cyi 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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [https://pdbe.org/5cyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [https://www.ebi.ac.uk/pdbsum/5cyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cyi ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:14, 21 June 2023

2023-06-21T10:14:27Z

←Older revision		Revision as of 10:14, 21 June 2023
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	==CDK2/Cyclin A covalent complex with 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)==		==CDK2/Cyclin A covalent complex with 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)==
-	<StructureSection load='5cyi' size='340' side='right' caption='[[5cyi]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5cyi' size='340' side='right'caption='[[5cyi]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5cyi]] is a 4 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=5CYI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5CYI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5cyi]] is a 4 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=5CYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CYI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [https://pdbe.org/5cyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [https://www.ebi.ac.uk/pdbsum/5cyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cyi ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2, CDKN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNA2, CCN1, CCNA ([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/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [~~http~~://pdbe.org/5cyi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5cyi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5cyi ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CDK2_HUMAN CDK2_HUMAN]] Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.<ref>PMID:10499802</ref> <ref>PMID:11051553</ref> <ref>PMID:10995386</ref> <ref>PMID:10995387</ref> <ref>PMID:10884347</ref> <ref>PMID:11113184</ref> <ref>PMID:15800615</ref> <ref>PMID:18372919</ref> <ref>PMID:20147522</ref> <ref>PMID:20079829</ref> <ref>PMID:20935635</ref> <ref>PMID:20195506</ref> <ref>PMID:19966300</ref> <ref>PMID:21262353</ref> <ref>PMID:21596315</ref> <ref>PMID:21319273</ref> <ref>PMID:17495531</ref> ~~[[http://www.uniprot.org/uniprot/CCNA2_HUMAN CCNA2_HUMAN]] Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.~~	+	[https://www.uniprot.org/uniprot/CDK2_HUMAN CDK2_HUMAN] Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.<ref>PMID:10499802</ref> <ref>PMID:11051553</ref> <ref>PMID:10995386</ref> <ref>PMID:10995387</ref> <ref>PMID:10884347</ref> <ref>PMID:11113184</ref> <ref>PMID:15800615</ref> <ref>PMID:18372919</ref> <ref>PMID:20147522</ref> <ref>PMID:20079829</ref> <ref>PMID:20935635</ref> <ref>PMID:20195506</ref> <ref>PMID:19966300</ref> <ref>PMID:21262353</ref> <ref>PMID:21596315</ref> <ref>PMID:21319273</ref> <ref>PMID:17495531</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5cyi" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5cyi" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cyclin 3D structures\|Cyclin 3D structures]]
		+	*[[Cyclin-dependent kinase 3D structures\|Cyclin-dependent kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cyclin-dependent kinase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Anscombe, E]]	+	[[Category: Anscombe E]]
-	[[Category: Cano, C]]	+	[[Category: Cano C]]
-	[[Category: Danielson~~, U H~~]]	+	[[Category: Danielson UH]]
-	[[Category: Endicott~~, J A~~]]	+	[[Category: Endicott JA]]
-	[[Category: Geitmann, M]]	+	[[Category: Geitmann M]]
-	[[Category: Golding~~, B T~~]]	+	[[Category: Golding BT]]
-	[[Category: Griffin~~, R J~~]]	+	[[Category: Griffin RJ]]
-	[[Category: Martin~~, M P~~]]	+	[[Category: Martin MP]]
-	[[Category: Meschini, E]]	+	[[Category: Meschini E]]
-	[[Category: Newell~~, D R~~]]	+	[[Category: Newell DR]]
-	[[Category: Noble~~, M E.M~~]]	+	[[Category: Noble MEM]]
-	[[Category: Reuillon, T]]	+	[[Category: Reuillon T]]
-	[[Category: Stanley~~, W A~~]]	+	[[Category: Stanley WA]]
-	[[Category: Staunton, D]]	+	[[Category: Staunton D]]
-	[[Category: Vidal~~, R M~~]]	+	[[Category: Vidal RM]]
-	[[Category: Wang~~, L Z~~]]	+	[[Category: Wang LZ]]
-	[[Category: Wedge~~, S R]]~~	+	[[Category: Wedge SR]]
-	~~[[Category: Cdk2 cyclin a covalent inhibitor vinylsulphone]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 17:18, 16 November 2017

2017-11-16T17:18:46Z

←Older revision		Revision as of 17:18, 16 November 2017
Line 1:		Line 1:
		+
	==CDK2/Cyclin A covalent complex with 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)==		==CDK2/Cyclin A covalent complex with 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)==
	<StructureSection load='5cyi' size='340' side='right' caption='[[5cyi]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5cyi' size='340' side='right' caption='[[5cyi]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5cyi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CYI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5cyi]] is a 4 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=5CYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CYI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2, CDKN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNA2, CCN1, CCNA ([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/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [http://pdbe.org/5cyi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [http://www.ebi.ac.uk/pdbsum/5cyi PDBsum]</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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [http://pdbe.org/5cyi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [http://www.ebi.ac.uk/pdbsum/5cyi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cyi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 24:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
		+	[[Category: Human]]
	[[Category: Anscombe, E]]		[[Category: Anscombe, E]]
	[[Category: Cano, C]]		[[Category: Cano, C]]

OCA at 07:00, 30 September 2015

2015-09-30T07:00:06Z

←Older revision		Revision as of 07:00, 30 September 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==CDK2/Cyclin A covalent complex with 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)==
		+	<StructureSection load='5cyi' size='340' side='right' caption='[[5cyi]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5cyi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CYI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CYI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=55S:6-(CYCLOHEXYLMETHOXY)-N-[4-(ETHYLSULFONYL)PHENYL]-9H-PURIN-2-AMINE'>55S</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] </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=5cyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cyi OCA], [http://pdbe.org/5cyi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cyi RCSB], [http://www.ebi.ac.uk/pdbsum/5cyi PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CDK2_HUMAN CDK2_HUMAN]] Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization.<ref>PMID:10499802</ref> <ref>PMID:11051553</ref> <ref>PMID:10995386</ref> <ref>PMID:10995387</ref> <ref>PMID:10884347</ref> <ref>PMID:11113184</ref> <ref>PMID:15800615</ref> <ref>PMID:18372919</ref> <ref>PMID:20147522</ref> <ref>PMID:20079829</ref> <ref>PMID:20935635</ref> <ref>PMID:20195506</ref> <ref>PMID:19966300</ref> <ref>PMID:21262353</ref> <ref>PMID:21596315</ref> <ref>PMID:21319273</ref> <ref>PMID:17495531</ref> [[http://www.uniprot.org/uniprot/CCNA2_HUMAN CCNA2_HUMAN]] Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds.

-	~~The entry 5cyi is ON HOLD~~	+	Identification and Characterization of an Irreversible Inhibitor of CDK2.,Anscombe E, Meschini E, Mora-Vidal R, Martin MP, Staunton D, Geitmann M, Danielson UH, Stanley WA, Wang LZ, Reuillon T, Golding BT, Cano C, Newell DR, Noble ME, Wedge SR, Endicott JA, Griffin RJ Chem Biol. 2015 Sep 17;22(9):1159-64. doi: 10.1016/j.chembiol.2015.07.018. Epub, 2015 Aug 27. PMID:26320860<ref>PMID:26320860</ref>

-	~~Authors: Anscombe, E., Meschini, E., Vidal, R.M., Martin, M.P., Staunton, D., Geitmann, M., Danielson~~, U.~~H., Stanley, W.A., Wang, L.Z., Reuillon, T., Golding, B.T., Cano, C., Newell, D.R., Noble, M.E.M., Wedge,~~ S.~~R., Endicott, J.A., Griffin, R.J~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: CDK2/Cyclin A covalent complex with 6~~-~~(cyclohexylmethoxy)~~-~~N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)~~	+	<div class="pdbe-citations 5cyi" style="background-color:#fffaf0;"></div>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	== References ==
-	~~[[Category: Endicott, J.A]]~~	+	<references/>
-	~~[[Category: Wedge, S.R]]~~	+	__TOC__
-	~~[[Category: Staunton, D]]~~	+	</StructureSection>
-	~~[[Category: Stanley, W.A]]~~	+	[[Category: Cyclin-dependent kinase]]
-	[[Category: ~~Golding, B.T~~]]	+	[[Category: Anscombe, E]]
-	[[Category: ~~Noble~~, M.E~~.M]]~~	+
-	~~[[Category: Wang, L.Z]]~~	+
-	~~[[Category: Meschini, E]]~~	+
-	~~[[Category: Danielson, U.H~~]]	+
	[[Category: Cano, C]]		[[Category: Cano, C]]
-	[[Category: ~~Martin~~, ~~M.P~~]]	+	[[Category: Danielson, U H]]
		+	[[Category: Endicott, J A]]
	[[Category: Geitmann, M]]		[[Category: Geitmann, M]]
-	[[Category: ~~Newell~~, ~~D.R~~]]	+	[[Category: Golding, B T]]
-	[[Category: Griffin, R.J]]	+	[[Category: Griffin, R J]]
-	[[Category: ~~Anscombe~~, E]]	+	[[Category: Martin, M P]]
		+	[[Category: Meschini, E]]
		+	[[Category: Newell, D R]]
		+	[[Category: Noble, M E.M]]
	[[Category: Reuillon, T]]		[[Category: Reuillon, T]]
-	[[Category: Vidal, R.M]]	+	[[Category: Stanley, W A]]
		+	[[Category: Staunton, D]]
		+	[[Category: Vidal, R M]]
		+	[[Category: Wang, L Z]]
		+	[[Category: Wedge, S R]]
		+	[[Category: Cdk2 cyclin a covalent inhibitor vinylsulphone]]
		+	[[Category: Transferase]]

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

2015-08-05T19:10:33Z

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

←Older revision

Revision as of 19:10, 5 August 2015

OCA: New page: '''Unreleased structure''' The entry 5cyi is ON HOLD Authors: Anscombe, E., Meschini, E., Vidal, R.M., Martin, M.P., Staunton, D., Geitmann, M., Danielson, U.H., Stanley, W.A., Wang, L....

2015-08-05T19:10:31Z

New page: '''Unreleased structure''' The entry 5cyi is ON HOLD Authors: Anscombe, E., Meschini, E., Vidal, R.M., Martin, M.P., Staunton, D., Geitmann, M., Danielson, U.H., Stanley, W.A., Wang, L....

New page

'''Unreleased structure'''

The entry 5cyi is ON HOLD

Authors: Anscombe, E., Meschini, E., Vidal, R.M., Martin, M.P., Staunton, D., Geitmann, M., Danielson, U.H., Stanley, W.A., Wang, L.Z., Reuillon, T., Golding, B.T., Cano, C., Newell, D.R., Noble, M.E.M., Wedge, S.R., Endicott, J.A., Griffin, R.J.

Description: CDK2/Cyclin A covalent complex with 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300)
[[Category: Unreleased Structures]]
[[Category: Endicott, J.A]]
[[Category: Wedge, S.R]]
[[Category: Staunton, D]]
[[Category: Stanley, W.A]]
[[Category: Golding, B.T]]
[[Category: Noble, M.E.M]]
[[Category: Wang, L.Z]]
[[Category: Meschini, E]]
[[Category: Danielson, U.H]]
[[Category: Cano, C]]
[[Category: Martin, M.P]]
[[Category: Geitmann, M]]
[[Category: Newell, D.R]]
[[Category: Griffin, R.J]]
[[Category: Anscombe, E]]
[[Category: Reuillon, T]]
[[Category: Vidal, R.M]]