3lfs - Revision history

OCA at 10:20, 21 February 2024

OCA — Wed, 21 Feb 2024 10:20:24 GMT

←Older revision		Revision as of 10:20, 21 February 2024
Line 1:		Line 1:

	==Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor==		==Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor==
-	<StructureSection load='3lfs' size='340' side='right' caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='3lfs' size='340' side='right'caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lfs]] 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=3LFS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3LFS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lfs]] 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=3LFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LFS FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</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]] 2.4Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fln\|3fln]]~~, [[~~3lfq~~\|~~3lfq~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [https://pdbe.org/3lfs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [https://www.ebi.ac.uk/pdbsum/3lfs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lfs ProSAT]</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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [~~http~~://pdbe.org/3lfs PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3lfs PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3lfs 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>	+	[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lfs ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lfs ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	From an HTS hit, a series of potent and selective inhibitors of GSK3beta have been designed based on a Cdk2-homology model and with the help of several crystal structures of the compounds within Cdk2.
-
-	Rational design of potent GSK3beta inhibitors with selectivity for Cdk1 and Cdk2.,Lesuisse D, Dutruc-Rosset G, Tiraboschi G, Dreyer MK, Maignan S, Chevalier A, Halley F, Bertrand P, Burgevin MC, Quarteronet D, Rooney T Bioorg Med Chem Lett. 2010 Mar 15;20(6):1985-9. Epub 2010 Jan 25. PMID:20167481<ref>PMID:20167481</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3lfs" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[Cyclin-dependent kinase\|Cyclin-dependent kinase]]	+	*[[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: Dreyer~~, M K~~]]	+	[[Category: Dreyer MK]]
-	[[Category: Loenze, P]]	+	[[Category: Loenze P]]
-	[[Category: Schimanski-Breves, S]]	+	[[Category: Schimanski-Breves S]]
-	[[Category: Wendt~~, K U]]~~	+	[[Category: Wendt KU]]
-	~~[[Category: Acetylation]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Cell division]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Mitosis]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Protein kinase fold]]~~	+
-	~~[[Category: Serine/threonine-protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:16, 2 January 2019

OCA — Wed, 02 Jan 2019 07:16:51 GMT

←Older revision		Revision as of 07:16, 2 January 2019
Line 1:		Line 1:
		+
	==Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor==		==Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor==
	<StructureSection load='3lfs' size='340' side='right' caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3lfs' size='340' side='right' caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://pdbe.org/3lfs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs 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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://pdbe.org/3lfs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lfs ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lf/3lfs_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lf/3lfs_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 43:		Line 44:
	[[Category: Schimanski-Breves, S]]		[[Category: Schimanski-Breves, S]]
	[[Category: Wendt, K U]]		[[Category: Wendt, K U]]
		+	[[Category: Acetylation]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
Line 50:		Line 52:
	[[Category: Nucleotide-binding]]		[[Category: Nucleotide-binding]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
		+	[[Category: Polymorphism]]
	[[Category: Protein kinase fold]]		[[Category: Protein kinase fold]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 11:51, 7 February 2016

OCA — Sun, 07 Feb 2016 11:51:18 GMT

←Older revision		Revision as of 11:51, 7 February 2016
Line 2:		Line 2:
	<StructureSection load='3lfs' size='340' side='right' caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3lfs' size='340' side='right' caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lfs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LFS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lfs]] 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=3LFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LFS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fln\|3fln]], [[3lfq\|3lfq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fln\|3fln]], [[3lfq\|3lfq]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs 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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://pdbe.org/3lfs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lfs ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3lfs" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[~~Cell division protein~~ kinase 2\|~~Cell division protein~~ kinase 2]]	+	*[[Cyclin-dependent kinase\|Cyclin-dependent kinase]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Dreyer, M K]]		[[Category: Dreyer, M K]]
	[[Category: Loenze, P]]		[[Category: Loenze, P]]

OCA at 14:52, 24 December 2014

OCA — Wed, 24 Dec 2014 14:52:21 GMT

←Older revision		Revision as of 14:52, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3lfs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LFS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3lfs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LFS FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fln\|3fln]], [[3lfq\|3lfq]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fln\|3fln]], [[3lfq\|3lfq]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs 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=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs PDBsum]</span></td></tr>
-	<table>	+	</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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 38:
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Dreyer, M K.]]	+	[[Category: Dreyer, M K]]
-	[[Category: Loenze, P.]]	+	[[Category: Loenze, P]]
-	[[Category: Schimanski-Breves, S.]]	+	[[Category: Schimanski-Breves, S]]
-	[[Category: Wendt, K U.]]	+	[[Category: Wendt, K U]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]

OCA at 11:19, 29 September 2014

OCA — Mon, 29 Sep 2014 11:19:54 GMT

←Older revision		Revision as of 11:19, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~3lfs.~~png~~\|~~left~~\|200px]]	+	==Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor==
		+	<StructureSection load='3lfs' size='340' side='right' caption='[[3lfs]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3lfs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LFS FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A07:N-(6-CHLORO-5-PHENYL-1H-INDAZOL-3-YL)BUTANAMIDE'>A07</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fln\|3fln]], [[3lfq\|3lfq]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lfs RCSB], [http://www.ebi.ac.uk/pdbsum/3lfs PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lf/3lfs_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	From an HTS hit, a series of potent and selective inhibitors of GSK3beta have been designed based on a Cdk2-homology model and with the help of several crystal structures of the compounds within Cdk2.

-	~~{{STRUCTURE_3lfs\| PDB=3lfs \| SCENE= }}~~	+	Rational design of potent GSK3beta inhibitors with selectivity for Cdk1 and Cdk2.,Lesuisse D, Dutruc-Rosset G, Tiraboschi G, Dreyer MK, Maignan S, Chevalier A, Halley F, Bertrand P, Burgevin MC, Quarteronet D, Rooney T Bioorg Med Chem Lett. 2010 Mar 15;20(6):1985-9. Epub 2010 Jan 25. PMID:20167481<ref>PMID:20167481</ref>

-	~~===Crystal structure of CDK2 with SAR37~~, ~~an aminoindazole type inhibitor===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20167481}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3lfs]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA].~~	+

	==See Also==		==See Also==
-	*[[Cell ~~Division Protein Kinase~~ 2\|Cell ~~Division Protein Kinase~~ 2]]	+	*[[Cell division protein kinase 2\|Cell division protein kinase 2]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020167481<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 06:33, 20 October 2012

OCA — Sat, 20 Oct 2012 06:33:10 GMT

←Older revision		Revision as of 06:33, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3lfs]] is a 1 chain structure ~~of [[Cell Division Protein Kinase 2]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA].	+	[[3lfs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA].

	==See Also==		==See Also==

OCA: Protected "3lfs" [edit=sysop:move=sysop]

OCA — Wed, 25 Jul 2012 13:33:06 GMT

Protected "3lfs" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:33, 25 July 2012

OCA at 13:33, 25 July 2012

OCA — Wed, 25 Jul 2012 13:33:04 GMT

←Older revision		Revision as of 13:33, 25 July 2012
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-	{{Seed}}
	[[Image:3lfs.png\|left\|200px]]		[[Image:3lfs.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_3lfs\| PDB=3lfs \| SCENE= }}		{{STRUCTURE_3lfs\| PDB=3lfs \| SCENE= }}

	===Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor===		===Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20167481}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20167481 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20167481}}		{{ABSTRACT_PUBMED_20167481}}

	==About this Structure==		==About this Structure==
-	~~3LFS~~ is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA].	+	[[3lfs]] is a 1 chain structure of [[Cell Division Protein Kinase 2]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA].
		+
		+	==See Also==
		+	*[[Cell Division Protein Kinase 2\|Cell Division Protein Kinase 2]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20167481~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020167481</ref><references group="xtra"/>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
Line 30:		Line 21:
	[[Category: Schimanski-Breves, S.]]		[[Category: Schimanski-Breves, S.]]
	[[Category: Wendt, K U.]]		[[Category: Wendt, K U.]]
-	[[Category: Acetylation]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
Line 38:		Line 28:
	[[Category: Nucleotide-binding]]		[[Category: Nucleotide-binding]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
-	[[Category: Polymorphism]]
	[[Category: Protein kinase fold]]		[[Category: Protein kinase fold]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 7 10:07:08 2010''

OCA at 07:07, 7 April 2010

OCA — Wed, 07 Apr 2010 07:07:09 GMT

←Older revision		Revision as of 07:07, 7 April 2010
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:3lfs.~~jpg~~\|left\|200px]]	+	[[Image:3lfs.png\|left\|200px]]

	<!--		<!--
Line 43:		Line 43:
	[[Category: Transferase]]		[[Category: Transferase]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Mar~~ ~~3 16~~:33:30 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 7 10:07:08 2010''

OCA at 14:33, 3 March 2010

OCA — Wed, 03 Mar 2010 14:33:32 GMT

←Older revision		Revision as of 14:33, 3 March 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3lfs.jpg\|left\|200px]]

-	The ~~entry 3lfs~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3lfs", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3lfs\| PDB=3lfs \| SCENE= }}

-	~~Authors: Dreyer~~, ~~M.K., Wendt, K.U., Schimanski-Breves, S., Loenze, P.~~	+	===Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor===

-	Description: Crystal structure of CDK2 with SAR37, an aminoindazole type inhibitor

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Feb~~ 3 09:19:17 2010''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20167481}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20167481 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20167481}}
		+
		+	==About this Structure==
		+	3LFS is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LFS OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20167481</ref><references group="xtra"/>
		+	[[Category: Cyclin-dependent kinase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Dreyer, M K.]]
		+	[[Category: Loenze, P.]]
		+	[[Category: Schimanski-Breves, S.]]
		+	[[Category: Wendt, K U.]]
		+	[[Category: Acetylation]]
		+	[[Category: Atp-binding]]
		+	[[Category: Cell cycle]]
		+	[[Category: Cell division]]
		+	[[Category: Kinase]]
		+	[[Category: Mitosis]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Polymorphism]]
		+	[[Category: Protein kinase fold]]
		+	[[Category: Serine/threonine-protein kinase]]
		+	[[Category: Transferase]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 3 16:33:30 2010''