3r8v - Revision history

OCA at 12:14, 14 March 2024

OCA — Thu, 14 Mar 2024 12:14:35 GMT

←Older revision		Revision as of 12:14, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3r8v' size='340' side='right'caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3r8v' size='340' side='right'caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r8v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r8v]] 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=3R8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R8V FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=Z62:[4~~-~~AMINO-2-(PROP-2-EN-1-YLAMINO)-1~~,~~3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</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]] 1.9Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; max-height: 3em;'>[[3ql8\|3ql8]], [[3qqf\|3qqf]], [[3qqg\|3qqg]], [[3qqh\|3qqh]], [[3qqj\|3qqj]], [[3qqk\|3qqk]], [[3qql\|3qql]], [[3qrt\|3qrt]], [[3qru\|3qru]], [[3qtq\|3qtq]], [[3qtr\|3qtr]], [[3qts\|3qts]], [[3qtu\|3qtu]], [[3qtw\|3qtw]], [[3qtx\|3qtx]], [[3qtz\|3qtz]], [[3qu0\|3qu0]], [[3qwj\|3qwj]], [[3qwk\|3qwk]], [[3qx2\|3qx2]], [[3qx4\|3qx4]], [[3qxo\|3qxo]], [[3qxp\|3qxp]], [[3qzf\|3qzf]], [[3qzg\|3qzg]], [[3qzh\|3qzh]], [[3qzi\|3qzi]], [[3r1q\|3r1q]], [[3r1s\|3r1s]], [[3r1y\|3r1y]], [[3r28\|3r28]], [[3r6x\|3r6x]], [[3r71\|3r71]], [[3r73\|3r73]], [[3r7e\|3r7e]], [[3r7i\|3r7i]], [[3r7u\|3r7u]], [[3r7v\|3r7v]], [[3r7y\|3r7y]], [[3r83\|3r83]], [[3r8l\|3r8l]], [[3r8m\|3r8m]], [[3r8p\|3r8p]], [[3r8u\|3r8u]], [[3r8z\|3r8z]], [[3r9d\|3r9d]], [[3r9h\|3r9h]], [[3r9n\|3r9n]], [[3r9o\|3r9o]], [[3rah\|3rah]], [[3rai\|3rai]], [[3rak\|3rak]], [[3ral\|3ral]], [[3rjc\|3rjc]], [[3rk5\|3rk5]], [[3rk7\|3rk7]], [[3rk9\|3rk9]], [[3rkb\|3rkb]], [[3rm6\|3rm6]], [[3rm7\|3rm7]], [[3rmf\|3rmf]], [[3rni\|3rni]], [[3roy\|3roy]], [[3rpo\|3rpo]], [[3rpr\|3rpr]], [[3rpv\|3rpv]], [[3rpy\|3rpy]], [[3rzb\|3rzb]], [[3s00\|3s00]], [[3s0o\|3s0o]], [[3s1h\|3s1h]], [[3sqq\|3sqq]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Z62:[4-AMINO-2-(PROP-2-EN-1-YLAMINO)-1,3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CDK2 ([https://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'>~~[~~https://en.wikipedia.org/wiki/Cyclin~~-~~dependent_kinase Cyclin~~-~~dependent kinase]~~, ~~with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [https://pdbe.org/3r8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [https://www.ebi.ac.uk/pdbsum/3r8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8v 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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [https://pdbe.org/3r8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [https://www.ebi.ac.uk/pdbsum/3r8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8v ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. Structure-based design was performed using 35 cocrystal structures of CDK2 liganded with distinct analogues of the parent compound. The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics.	+
-		+
-	Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases.,Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI J Med Chem. 2013 May 6. PMID:23600925<ref>PMID:23600925</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3r8v" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 28:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cyclin-dependent kinase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Alam, R]]	+	[[Category: Alam R]]
-	[[Category: Becker, A]]	+	[[Category: Becker A]]
-	[[Category: Betzi, S]]	+	[[Category: Betzi S]]
-	[[Category: Han, H]]	+	[[Category: Han H]]
-	[[Category: Schonbrunn, E]]	+	[[Category: Schonbrunn E]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 05:53, 15 June 2022

OCA — Wed, 15 Jun 2022 05:53:36 GMT

←Older revision		Revision as of 05:53, 15 June 2022
Line 1:		Line 1:

	==CDK2 in complex with inhibitor RC-1-135==		==CDK2 in complex with inhibitor RC-1-135==
-	<StructureSection load='3r8v' size='340' side='right' caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='3r8v' size='340' side='right'caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r8v]] 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=3R8V OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3R8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r8v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R8V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z62:[4-AMINO-2-(PROP-2-EN-1-YLAMINO)-1,3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Z62:[4-AMINO-2-(PROP-2-EN-1-YLAMINO)-1,3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ql8\|3ql8]], [[3qqf\|3qqf]], [[3qqg\|3qqg]], [[3qqh\|3qqh]], [[3qqj\|3qqj]], [[3qqk\|3qqk]], [[3qql\|3qql]], [[3qrt\|3qrt]], [[3qru\|3qru]], [[3qtq\|3qtq]], [[3qtr\|3qtr]], [[3qts\|3qts]], [[3qtu\|3qtu]], [[3qtw\|3qtw]], [[3qtx\|3qtx]], [[3qtz\|3qtz]], [[3qu0\|3qu0]], [[3qwj\|3qwj]], [[3qwk\|3qwk]], [[3qx2\|3qx2]], [[3qx4\|3qx4]], [[3qxo\|3qxo]], [[3qxp\|3qxp]], [[3qzf\|3qzf]], [[3qzg\|3qzg]], [[3qzh\|3qzh]], [[3qzi\|3qzi]], [[3r1q\|3r1q]], [[3r1s\|3r1s]], [[3r1y\|3r1y]], [[3r28\|3r28]], [[3r6x\|3r6x]], [[3r71\|3r71]], [[3r73\|3r73]], [[3r7e\|3r7e]], [[3r7i\|3r7i]], [[3r7u\|3r7u]], [[3r7v\|3r7v]], [[3r7y\|3r7y]], [[3r83\|3r83]], [[3r8l\|3r8l]], [[3r8m\|3r8m]], [[3r8p\|3r8p]], [[3r8u\|3r8u]], [[3r8z\|3r8z]], [[3r9d\|3r9d]], [[3r9h\|3r9h]], [[3r9n\|3r9n]], [[3r9o\|3r9o]], [[3rah\|3rah]], [[3rai\|3rai]], [[3rak\|3rak]], [[3ral\|3ral]], [[3rjc\|3rjc]], [[3rk5\|3rk5]], [[3rk7\|3rk7]], [[3rk9\|3rk9]], [[3rkb\|3rkb]], [[3rm6\|3rm6]], [[3rm7\|3rm7]], [[3rmf\|3rmf]], [[3rni\|3rni]], [[3roy\|3roy]], [[3rpo\|3rpo]], [[3rpr\|3rpr]], [[3rpv\|3rpv]], [[3rpy\|3rpy]], [[3rzb\|3rzb]], [[3s00\|3s00]], [[3s0o\|3s0o]], [[3s1h\|3s1h]], [[3sqq\|3sqq]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ql8\|3ql8]], [[3qqf\|3qqf]], [[3qqg\|3qqg]], [[3qqh\|3qqh]], [[3qqj\|3qqj]], [[3qqk\|3qqk]], [[3qql\|3qql]], [[3qrt\|3qrt]], [[3qru\|3qru]], [[3qtq\|3qtq]], [[3qtr\|3qtr]], [[3qts\|3qts]], [[3qtu\|3qtu]], [[3qtw\|3qtw]], [[3qtx\|3qtx]], [[3qtz\|3qtz]], [[3qu0\|3qu0]], [[3qwj\|3qwj]], [[3qwk\|3qwk]], [[3qx2\|3qx2]], [[3qx4\|3qx4]], [[3qxo\|3qxo]], [[3qxp\|3qxp]], [[3qzf\|3qzf]], [[3qzg\|3qzg]], [[3qzh\|3qzh]], [[3qzi\|3qzi]], [[3r1q\|3r1q]], [[3r1s\|3r1s]], [[3r1y\|3r1y]], [[3r28\|3r28]], [[3r6x\|3r6x]], [[3r71\|3r71]], [[3r73\|3r73]], [[3r7e\|3r7e]], [[3r7i\|3r7i]], [[3r7u\|3r7u]], [[3r7v\|3r7v]], [[3r7y\|3r7y]], [[3r83\|3r83]], [[3r8l\|3r8l]], [[3r8m\|3r8m]], [[3r8p\|3r8p]], [[3r8u\|3r8u]], [[3r8z\|3r8z]], [[3r9d\|3r9d]], [[3r9h\|3r9h]], [[3r9n\|3r9n]], [[3r9o\|3r9o]], [[3rah\|3rah]], [[3rai\|3rai]], [[3rak\|3rak]], [[3ral\|3ral]], [[3rjc\|3rjc]], [[3rk5\|3rk5]], [[3rk7\|3rk7]], [[3rk9\|3rk9]], [[3rkb\|3rkb]], [[3rm6\|3rm6]], [[3rm7\|3rm7]], [[3rmf\|3rmf]], [[3rni\|3rni]], [[3roy\|3roy]], [[3rpo\|3rpo]], [[3rpr\|3rpr]], [[3rpv\|3rpv]], [[3rpy\|3rpy]], [[3rzb\|3rzb]], [[3s00\|3s00]], [[3s0o\|3s0o]], [[3s1h\|3s1h]], [[3sqq\|3sqq]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDK2 ([https://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'>[https://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [https://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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [~~http~~://pdbe.org/3r8v PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3r8v PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8v 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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [https://pdbe.org/3r8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [https://www.ebi.ac.uk/pdbsum/3r8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8v 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 23:		Line 23:

	==See Also==		==See Also==
-	*[[Cyclin-dependent kinase\|Cyclin-dependent kinase]]	+	*[[Cyclin-dependent kinase 3D structures\|Cyclin-dependent kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 30:
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Alam, R]]		[[Category: Alam, R]]
	[[Category: Becker, A]]		[[Category: Becker, A]]

OCA at 22:33, 5 August 2016

OCA — Fri, 05 Aug 2016 22:33:56 GMT

←Older revision		Revision as of 22:33, 5 August 2016
Line 1:		Line 1:
		+
	==CDK2 in complex with inhibitor RC-1-135==		==CDK2 in complex with inhibitor RC-1-135==
	<StructureSection load='3r8v' size='340' side='right' caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3r8v' size='340' side='right' caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r8v]] 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=3R8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r8v]] 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=3R8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R8V FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z62:[4-AMINO-2-(PROP-2-EN-1-YLAMINO)-1,3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z62:[4-AMINO-2-(PROP-2-EN-1-YLAMINO)-1,3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ql8\|3ql8]], [[3qqf\|3qqf]], [[3qqg\|3qqg]], [[3qqh\|3qqh]], [[3qqj\|3qqj]], [[3qqk\|3qqk]], [[3qql\|3qql]], [[3qrt\|3qrt]], [[3qru\|3qru]], [[3qtq\|3qtq]], [[3qtr\|3qtr]], [[3qts\|3qts]], [[3qtu\|3qtu]], [[3qtw\|3qtw]], [[3qtx\|3qtx]], [[3qtz\|3qtz]], [[3qu0\|3qu0]], [[3qwj\|3qwj]], [[3qwk\|3qwk]], [[3qx2\|3qx2]], [[3qx4\|3qx4]], [[3qxo\|3qxo]], [[3qxp\|3qxp]], [[3qzf\|3qzf]], [[3qzg\|3qzg]], [[3qzh\|3qzh]], [[3qzi\|3qzi]], [[3r1q\|3r1q]], [[3r1s\|3r1s]], [[3r1y\|3r1y]], [[3r28\|3r28]], [[3r6x\|3r6x]], [[3r71\|3r71]], [[3r73\|3r73]], [[3r7e\|3r7e]], [[3r7i\|3r7i]], [[3r7u\|3r7u]], [[3r7v\|3r7v]], [[3r7y\|3r7y]], [[3r83\|3r83]], [[3r8l\|3r8l]], [[3r8m\|3r8m]], [[3r8p\|3r8p]], [[3r8u\|3r8u]], [[3r8z\|3r8z]], [[3r9d\|3r9d]], [[3r9h\|3r9h]], [[3r9n\|3r9n]], [[3r9o\|3r9o]], [[3rah\|3rah]], [[3rai\|3rai]], [[3rak\|3rak]], [[3ral\|3ral]], [[3rjc\|3rjc]], [[3rk5\|3rk5]], [[3rk7\|3rk7]], [[3rk9\|3rk9]], [[3rkb\|3rkb]], [[3rm6\|3rm6]], [[3rm7\|3rm7]], [[3rmf\|3rmf]], [[3rni\|3rni]], [[3roy\|3roy]], [[3rpo\|3rpo]], [[3rpr\|3rpr]], [[3rpv\|3rpv]], [[3rpy\|3rpy]], [[3rzb\|3rzb]], [[3s00\|3s00]], [[3s0o\|3s0o]], [[3s1h\|3s1h]], [[3sqq\|3sqq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ql8\|3ql8]], [[3qqf\|3qqf]], [[3qqg\|3qqg]], [[3qqh\|3qqh]], [[3qqj\|3qqj]], [[3qqk\|3qqk]], [[3qql\|3qql]], [[3qrt\|3qrt]], [[3qru\|3qru]], [[3qtq\|3qtq]], [[3qtr\|3qtr]], [[3qts\|3qts]], [[3qtu\|3qtu]], [[3qtw\|3qtw]], [[3qtx\|3qtx]], [[3qtz\|3qtz]], [[3qu0\|3qu0]], [[3qwj\|3qwj]], [[3qwk\|3qwk]], [[3qx2\|3qx2]], [[3qx4\|3qx4]], [[3qxo\|3qxo]], [[3qxp\|3qxp]], [[3qzf\|3qzf]], [[3qzg\|3qzg]], [[3qzh\|3qzh]], [[3qzi\|3qzi]], [[3r1q\|3r1q]], [[3r1s\|3r1s]], [[3r1y\|3r1y]], [[3r28\|3r28]], [[3r6x\|3r6x]], [[3r71\|3r71]], [[3r73\|3r73]], [[3r7e\|3r7e]], [[3r7i\|3r7i]], [[3r7u\|3r7u]], [[3r7v\|3r7v]], [[3r7y\|3r7y]], [[3r83\|3r83]], [[3r8l\|3r8l]], [[3r8m\|3r8m]], [[3r8p\|3r8p]], [[3r8u\|3r8u]], [[3r8z\|3r8z]], [[3r9d\|3r9d]], [[3r9h\|3r9h]], [[3r9n\|3r9n]], [[3r9o\|3r9o]], [[3rah\|3rah]], [[3rai\|3rai]], [[3rak\|3rak]], [[3ral\|3ral]], [[3rjc\|3rjc]], [[3rk5\|3rk5]], [[3rk7\|3rk7]], [[3rk9\|3rk9]], [[3rkb\|3rkb]], [[3rm6\|3rm6]], [[3rm7\|3rm7]], [[3rmf\|3rmf]], [[3rni\|3rni]], [[3roy\|3roy]], [[3rpo\|3rpo]], [[3rpr\|3rpr]], [[3rpv\|3rpv]], [[3rpy\|3rpy]], [[3rzb\|3rzb]], [[3s00\|3s00]], [[3s0o\|3s0o]], [[3s1h\|3s1h]], [[3sqq\|3sqq]]</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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [http://www.ebi.ac.uk/pdbsum/3r8v 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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [http://pdbe.org/3r8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [http://www.ebi.ac.uk/pdbsum/3r8v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8v ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3r8v" 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 27:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Alam, R]]		[[Category: Alam, R]]
	[[Category: Becker, A]]		[[Category: Becker, A]]

OCA at 22:30, 25 December 2014

OCA — Thu, 25 Dec 2014 22:30:09 GMT

←Older revision		Revision as of 22:30, 25 December 2014
Line 9:		Line 9:
	<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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [http://www.ebi.ac.uk/pdbsum/3r8v 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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [http://www.ebi.ac.uk/pdbsum/3r8v 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:24, 19 December 2014

OCA — Fri, 19 Dec 2014 10:24:22 GMT

←Older revision		Revision as of 10:24, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3r8v~~\| ~~PDB~~=3r8v \| ~~SCENE~~= }}	+	==CDK2 in complex with inhibitor RC-1-135==
-	===CDK2 ~~in complex~~ with ~~inhibitor RC~~-1-~~135~~===	+	<StructureSection load='3r8v' size='340' side='right' caption='[[3r8v]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23600925}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3r8v]] 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=3R8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R8V FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z62:[4-AMINO-2-(PROP-2-EN-1-YLAMINO)-1,3-THIAZOL-5-YL](3-NITROPHENYL)METHANONE'>Z62</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ql8\|3ql8]], [[3qqf\|3qqf]], [[3qqg\|3qqg]], [[3qqh\|3qqh]], [[3qqj\|3qqj]], [[3qqk\|3qqk]], [[3qql\|3qql]], [[3qrt\|3qrt]], [[3qru\|3qru]], [[3qtq\|3qtq]], [[3qtr\|3qtr]], [[3qts\|3qts]], [[3qtu\|3qtu]], [[3qtw\|3qtw]], [[3qtx\|3qtx]], [[3qtz\|3qtz]], [[3qu0\|3qu0]], [[3qwj\|3qwj]], [[3qwk\|3qwk]], [[3qx2\|3qx2]], [[3qx4\|3qx4]], [[3qxo\|3qxo]], [[3qxp\|3qxp]], [[3qzf\|3qzf]], [[3qzg\|3qzg]], [[3qzh\|3qzh]], [[3qzi\|3qzi]], [[3r1q\|3r1q]], [[3r1s\|3r1s]], [[3r1y\|3r1y]], [[3r28\|3r28]], [[3r6x\|3r6x]], [[3r71\|3r71]], [[3r73\|3r73]], [[3r7e\|3r7e]], [[3r7i\|3r7i]], [[3r7u\|3r7u]], [[3r7v\|3r7v]], [[3r7y\|3r7y]], [[3r83\|3r83]], [[3r8l\|3r8l]], [[3r8m\|3r8m]], [[3r8p\|3r8p]], [[3r8u\|3r8u]], [[3r8z\|3r8z]], [[3r9d\|3r9d]], [[3r9h\|3r9h]], [[3r9n\|3r9n]], [[3r9o\|3r9o]], [[3rah\|3rah]], [[3rai\|3rai]], [[3rak\|3rak]], [[3ral\|3ral]], [[3rjc\|3rjc]], [[3rk5\|3rk5]], [[3rk7\|3rk7]], [[3rk9\|3rk9]], [[3rkb\|3rkb]], [[3rm6\|3rm6]], [[3rm7\|3rm7]], [[3rmf\|3rmf]], [[3rni\|3rni]], [[3roy\|3roy]], [[3rpo\|3rpo]], [[3rpr\|3rpr]], [[3rpv\|3rpv]], [[3rpy\|3rpy]], [[3rzb\|3rzb]], [[3s00\|3s00]], [[3s0o\|3s0o]], [[3s1h\|3s1h]], [[3sqq\|3sqq]]</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='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=3r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r8v RCSB], [http://www.ebi.ac.uk/pdbsum/3r8v PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. Structure-based design was performed using 35 cocrystal structures of CDK2 liganded with distinct analogues of the parent compound. The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics.

-	~~==Function==~~	+	Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases.,Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI J Med Chem. 2013 May 6. PMID:23600925<ref>PMID:23600925</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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3r8v]] 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=3R8V OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023600925</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: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Alam, R.]]	+	[[Category: Alam, R]]
-	[[Category: Becker, A.]]	+	[[Category: Becker, A]]
-	[[Category: Betzi, S.]]	+	[[Category: Betzi, S]]
-	[[Category: Han, H.]]	+	[[Category: Han, H]]
-	[[Category: Schonbrunn, E.]]	+	[[Category: Schonbrunn, E]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Protein kinase]]		[[Category: Protein kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 18:20, 19 June 2013

OCA — Wed, 19 Jun 2013 18:20:09 GMT

←Older revision		Revision as of 18:20, 19 June 2013
Line 10:		Line 10:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023600925</ref><references group="xtra"/><references/>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 06:04, 16 May 2013

OCA — Thu, 16 May 2013 06:04:56 GMT

←Older revision		Revision as of 06:04, 16 May 2013
Line 1:		Line 1:
-	[[Image:3r8v.jpg\|left\|200px]]
-
	{{STRUCTURE_3r8v\| PDB=3r8v \| SCENE= }}		{{STRUCTURE_3r8v\| PDB=3r8v \| SCENE= }}
-
	===CDK2 in complex with inhibitor RC-1-135===		===CDK2 in complex with inhibitor RC-1-135===
		+	{{ABSTRACT_PUBMED_23600925}}

		+	==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>

	==About this Structure==		==About this Structure==
	[[3r8v]] 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=3R8V OCA].		[[3r8v]] 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=3R8V OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Cyclin-dependent kinase]]		[[Category: Cyclin-dependent kinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 09:14, 31 October 2012

OCA — Wed, 31 Oct 2012 09:14:10 GMT

←Older revision		Revision as of 09:14, 31 October 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3r8v.jpg\|left\|200px]]

-	~~The entry~~ 3r8v ~~is ON HOLD~~ ~~until Oct 31 2013~~	+	{{STRUCTURE_3r8v\| PDB=3r8v \| SCENE= }}

-	~~Authors: Betzi, S., Alam, R., Han, H., Becker, A., Schonbrunn, E.~~	+	===CDK2 in complex with inhibitor RC-1-135===

-	~~Description: CDK2 in complex~~ with ~~inhibitor RC~~-1-~~135~~	+
		+	==About this Structure==
		+	[[3r8v]] 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=3R8V OCA].
		+	[[Category: Cyclin-dependent kinase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Alam, R.]]
		+	[[Category: Becker, A.]]
		+	[[Category: Betzi, S.]]
		+	[[Category: Han, H.]]
		+	[[Category: Schonbrunn, E.]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:37, 19 September 2012

OCA — Wed, 19 Sep 2012 06:37:41 GMT

←Older revision		Revision as of 06:37, 19 September 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3r8v is ON HOLD until ~~Sep 26~~ 2013	+	The entry 3r8v is ON HOLD until Oct 31 2013

	Authors: Betzi, S., Alam, R., Han, H., Becker, A., Schonbrunn, E.		Authors: Betzi, S., Alam, R., Han, H., Becker, A., Schonbrunn, E.

	Description: CDK2 in complex with inhibitor RC-1-135		Description: CDK2 in complex with inhibitor RC-1-135

OCA at 04:46, 18 July 2012

OCA — Wed, 18 Jul 2012 04:46:59 GMT

←Older revision		Revision as of 04:46, 18 July 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3r8v is ON HOLD until ~~Aug 01~~ 2013	+	The entry 3r8v is ON HOLD until Sep 26 2013

	Authors: Betzi, S., Alam, R., Han, H., Becker, A., Schonbrunn, E.		Authors: Betzi, S., Alam, R., Han, H., Becker, A., Schonbrunn, E.

	Description: CDK2 in complex with inhibitor RC-1-135		Description: CDK2 in complex with inhibitor RC-1-135