4kd1 - Revision history

OCA at 15:57, 20 September 2023

OCA — Wed, 20 Sep 2023 15:57:59 GMT

←Older revision		Revision as of 15:57, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4kd1]] 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=4KD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KD1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4kd1]] 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=4KD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KD1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QK:3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1-HYDROXYPYRIDINIUM'>1QK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QK:3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1-HYDROXYPYRIDINIUM'>1QK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [https://pdbe.org/4kd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [https://www.ebi.ac.uk/pdbsum/4kd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kd1 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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [https://pdbe.org/4kd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [https://www.ebi.ac.uk/pdbsum/4kd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kd1 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 11:52, 30 November 2022

OCA — Wed, 30 Nov 2022 11:52:48 GMT

←Older revision		Revision as of 11:52, 30 November 2022
Line 1:		Line 1:

	==CDK2 in complex with Dinaciclib==		==CDK2 in complex with Dinaciclib==
-	<StructureSection load='4kd1' size='340' side='right' caption='[[4kd1]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='4kd1' size='340' side='right'caption='[[4kd1]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4kd1]] 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=4KD1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4KD1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4kd1]] 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=4KD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KD1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QK:3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1-HYDROXYPYRIDINIUM'>1QK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QK:3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1-HYDROXYPYRIDINIUM'>1QK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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])</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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [https://pdbe.org/4kd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [https://www.ebi.ac.uk/pdbsum/4kd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kd1 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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [~~http~~://pdbe.org/4kd1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4kd1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4kd1 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==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: Martin~~, M P~~]]	+	[[Category: Martin MP]]
-	[[Category: Schonbrunn, E]]	+	[[Category: Schonbrunn E]]
-	~~[[Category: Cell cycle-inhibitor complex]]~~	+
-	~~[[Category: Dinaciclib]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase~~]]	+

OCA at 11:12, 4 August 2016

OCA — Thu, 04 Aug 2016 11:12:18 GMT

←Older revision		Revision as of 11:12, 4 August 2016
Line 1:		Line 1:
		+
	==CDK2 in complex with Dinaciclib==		==CDK2 in complex with Dinaciclib==
	<StructureSection load='4kd1' size='340' side='right' caption='[[4kd1]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='4kd1' size='340' side='right' caption='[[4kd1]], [[Resolution\|resolution]] 1.70Å' scene=''>
Line 6:		Line 7:
	<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])</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])</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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [http://www.ebi.ac.uk/pdbsum/4kd1 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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [http://pdbe.org/4kd1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [http://www.ebi.ac.uk/pdbsum/4kd1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kd1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4kd1" 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/>

OCA at 13:42, 24 December 2014

OCA — Wed, 24 Dec 2014 13:42:55 GMT

←Older revision		Revision as of 13:42, 24 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4kd1~~\| ~~PDB~~=4kd1 \| ~~SCENE~~= }}	+	==CDK2 in complex with Dinaciclib==
-	===CDK2 ~~in complex with Dinaciclib~~===	+	<StructureSection load='4kd1' size='340' side='right' caption='[[4kd1]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24007471}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4kd1]] 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=4KD1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KD1 FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QK:3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1-HYDROXYPYRIDINIUM'>1QK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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])</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=4kd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kd1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kd1 RCSB], [http://www.ebi.ac.uk/pdbsum/4kd1 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/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;">
		+	== Publication Abstract from PubMed ==
		+	Bromodomain-containing proteins are considered atypical kinases, but their potential to interact with kinase inhibitors is unknown. Dinaciclib is a potent inhibitor of cyclin-dependent kinases (CDKs), which recently advanced to Phase III clinical trials for the treatment of leukemia. We determined the crystal structure of dinaciclib in complex with CDK2 at 1.7 A resolution, revealing an elaborate network of binding interactions in the ATP site, which explains the extraordinary potency and selectivity of this inhibitor. Remarkably, dinaciclib also interacted with the acetyl-lysine recognition site of the bromodomain testis-specific protein BRDT, a member of the BET family of bromodomains. The binding mode of dinaciclib to BRDT at 2.0 A resolution suggests that general kinase inhibitors ("hinge binders") possess a previously unrecognized potential to act as protein-protein inhibitors of bromodomains. The findings may provide a new structural framework for the design of next-generation bromodomain inhibitors using the vast chemical space of kinase inhibitors.
		+
		+	Cyclin-Dependent Kinase Inhibitor Dinaciclib Interacts with the Acetyl-Lysine Recognition Site of Bromodomains.,Martin MP, Olesen SH, Georg GI, Schonbrunn E ACS Chem Biol. 2013 Sep 10. PMID:24007471<ref>PMID:24007471</ref>

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4kd1]] 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=4KD1 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024007471</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Cell division protein kinase 2\|Cell division protein kinase 2]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Martin, M P.]]	+	[[Category: Martin, M P]]
-	[[Category: Schonbrunn, E.]]	+	[[Category: Schonbrunn, E]]
	[[Category: Cell cycle-inhibitor complex]]		[[Category: Cell cycle-inhibitor complex]]
	[[Category: Dinaciclib]]		[[Category: Dinaciclib]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Transferase-transferase]]		[[Category: Transferase-transferase]]

OCA at 08:31, 25 December 2013

OCA — Wed, 25 Dec 2013 08:31:47 GMT

←Older revision		Revision as of 08:31, 25 December 2013
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4kd1]] 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=4KD1 OCA].	+	[[4kd1]] 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=4KD1 OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024007471</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024007471</ref><references group="xtra"/><references/>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Martin, M P.]]		[[Category: Martin, M P.]]
	[[Category: Schonbrunn, E.]]		[[Category: Schonbrunn, E.]]

OCA at 04:07, 20 September 2013

OCA — Fri, 20 Sep 2013 04:07:35 GMT

←Older revision		Revision as of 04:07, 20 September 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4kd1\| PDB=4kd1 \| SCENE= }}
		+	===CDK2 in complex with Dinaciclib===
		+	{{ABSTRACT_PUBMED_24007471}}

-	~~The~~ entry ~~4kd1~~ is ~~ON HOLD~~ until ~~Paper Publication~~	+	==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>

-	~~Authors~~: ~~Martin, M~~.P.~~, Schonbrunn, E~~.	+	==About this Structure==
		+	[[4kd1]] 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=4KD1 OCA].

-	~~Description~~: ~~CDK2 in~~ complex ~~with~~ Dinaciclib	+	==Reference==
		+	<ref group="xtra">PMID:024007471</ref><references group="xtra"/><references/>
		+	[[Category: Cyclin-dependent kinase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Martin, M P.]]
		+	[[Category: Schonbrunn, E.]]
		+	[[Category: Cell cycle-inhibitor complex]]
		+	[[Category: Dinaciclib]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase]]

OCA at 07:20, 8 May 2013

OCA — Wed, 08 May 2013 07:20:38 GMT

←Older revision		Revision as of 07:20, 8 May 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4kd1 is ON HOLD	+	The entry 4kd1 is ON HOLD until Paper Publication

	Authors: Martin, M.P., Schonbrunn, E.		Authors: Martin, M.P., Schonbrunn, E.

	Description: CDK2 in complex with Dinaciclib		Description: CDK2 in complex with Dinaciclib

OCA: Protected "4kd1" [edit=sysop:move=sysop]

OCA — Thu, 02 May 2013 07:16:53 GMT

Protected "4kd1" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:16, 2 May 2013

OCA: New page: '''Unreleased structure''' The entry 4kd1 is ON HOLD Authors: Martin, M.P., Schonbrunn, E. Description: CDK2 in complex with Dinaciclib

OCA — Thu, 02 May 2013 07:16:52 GMT

New page: '''Unreleased structure''' The entry 4kd1 is ON HOLD Authors: Martin, M.P., Schonbrunn, E. Description: CDK2 in complex with Dinaciclib

New page

'''Unreleased structure'''

The entry 4kd1 is ON HOLD

Authors: Martin, M.P., Schonbrunn, E.

Description: CDK2 in complex with Dinaciclib