2xez - Revision history

OCA at 10:30, 20 December 2023

OCA — Wed, 20 Dec 2023 10:30:14 GMT

←Older revision		Revision as of 10:30, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='2xez' size='340' side='right'caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='2xez' size='340' side='right'caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=EDO:1,2~~-~~ETHANEDIOL'>EDO</scene>~~, ~~<scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO~~[1,2~~-A]PYRAZINE'>XEZ</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]] 2.25Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non~~-~~specific_serine/threonine_protein_kinase Non~~-~~specific serine/threonine protein kinase], with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.7.11.~~1 2~~.7.11.1~~] </~~span~~></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [https://pdbe.org/2xez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [https://www.ebi.ac.uk/pdbsum/2xez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xez 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=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [https://pdbe.org/2xez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [https://www.ebi.ac.uk/pdbsum/2xez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xez ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CHK1_HUMAN CHK1_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref> Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref>	+	[https://www.uniprot.org/uniprot/CHK1_HUMAN CHK1_HUMAN] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref> Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Addison GJ]]
-	[[Category: Addison~~, G J~~]]	+	[[Category: Aherne GW]]
-	[[Category: Aherne~~, G W~~]]	+	[[Category: Allen CE]]
-	[[Category: Allen~~, C E~~]]	+	[[Category: Boxall K]]
-	[[Category: Boxall, K]]	+	[[Category: Cherry M]]
-	[[Category: Cherry, M]]	+	[[Category: Collins I]]
-	[[Category: Collins, I]]	+	[[Category: Ellard J]]
-	[[Category: Ellard, J]]	+	[[Category: Fisher M]]
-	[[Category: Fisher, M]]	+	[[Category: Garrett MD]]
-	[[Category: Garrett~~, M D~~]]	+	[[Category: Klair S]]
-	[[Category: Klair, S]]	+	[[Category: Matthews TP]]
-	[[Category: Matthews~~, T P~~]]	+	[[Category: McHardy T]]
-	[[Category: McHardy, T]]	+	[[Category: Reader JC]]
-	[[Category: Reader~~, J C~~]]	+	[[Category: Westwood IM]]
-	[[Category: Westwood~~, I M~~]]	+	[[Category: VanMontfort R]]
-	[[Category: VanMontfort, R]]	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:39, 10 November 2021

OCA — Wed, 10 Nov 2021 08:39:14 GMT

←Older revision		Revision as of 08:39, 10 November 2021
Line 3:		Line 3:
	<StructureSection load='2xez' size='340' side='right'caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='2xez' size='340' side='right'caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</div></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [~~http~~://pdbe.org/2xez PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2xez PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2xez 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=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [https://pdbe.org/2xez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [https://www.ebi.ac.uk/pdbsum/2xez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xez ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CHK1_HUMAN CHK1_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref> Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref>	+	[[https://www.uniprot.org/uniprot/CHK1_HUMAN CHK1_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref> Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]	+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:03, 7 August 2019

OCA — Wed, 07 Aug 2019 07:03:49 GMT

←Older revision		Revision as of 07:03, 7 August 2019
Line 1:		Line 1:

	==Crystal structure of checkpoint kinase 1 (Chk1) in complex with inhibitors==		==Crystal structure of checkpoint kinase 1 (Chk1) in complex with inhibitors==
-	<StructureSection load='2xez' size='340' side='right' caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>	+	<StructureSection load='2xez' size='340' side='right'caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
Line 15:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xe/2xez_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xe/2xez_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 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 2xez" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2xez" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Addison, G J]]		[[Category: Addison, G J]]

OCA at 12:08, 6 November 2017

OCA — Mon, 06 Nov 2017 12:08:36 GMT

←Older revision		Revision as of 12:08, 6 November 2017
Line 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 2xez" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2xez" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:22, 3 August 2017

OCA — Thu, 03 Aug 2017 09:22:21 GMT

←Older revision		Revision as of 09:22, 3 August 2017
Line 1:		Line 1:

-	==~~CRYSTAL STRUCTURE OF CHECKPOINT KINASE~~ 1 (~~CHK1~~) ~~IN COMPLEX WITH INHIBITORS~~==	+	==Crystal structure of checkpoint kinase 1 (Chk1) in complex with inhibitors==
	<StructureSection load='2xez' size='340' side='right' caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='2xez' size='340' side='right' caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xez]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>
Line 37:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Addison, G J]]		[[Category: Addison, G J]]
Line 50:		Line 49:
	[[Category: Klair, S]]		[[Category: Klair, S]]
	[[Category: Matthews, T P]]		[[Category: Matthews, T P]]
-	[[Category: ~~Mchardy~~, T]]	+	[[Category: McHardy, T]]
	[[Category: Reader, J C]]		[[Category: Reader, J C]]
-	[[Category: Vanmontfort, R]]
	[[Category: Westwood, I M]]		[[Category: Westwood, I M]]
		+	[[Category: VanMontfort, R]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Dna repair]]		[[Category: Dna repair]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:01, 5 August 2016

OCA — Fri, 05 Aug 2016 19:01:59 GMT

←Older revision		Revision as of 19:01, 5 August 2016
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS==		==CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS==
	<StructureSection load='2xez' size='340' side='right' caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='2xez' size='340' side='right' caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [http://www.ebi.ac.uk/pdbsum/2xez 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=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [http://pdbe.org/2xez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [http://www.ebi.ac.uk/pdbsum/2xez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xez ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		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=2xez ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		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 2xez" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Addison, G J]]		[[Category: Addison, G J]]

OCA at 05:02, 25 December 2014

OCA — Thu, 25 Dec 2014 05:02:26 GMT

←Older revision		Revision as of 05:02, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [http://www.ebi.ac.uk/pdbsum/2xez 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=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [http://www.ebi.ac.uk/pdbsum/2xez PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CHK1_HUMAN CHK1_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref> Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.<ref>PMID:9278511</ref> <ref>PMID:10673501</ref> <ref>PMID:11535615</ref> <ref>PMID:12446774</ref> <ref>PMID:12399544</ref> <ref>PMID:12676583</ref> <ref>PMID:12660173</ref> <ref>PMID:14681206</ref> <ref>PMID:12676925</ref> <ref>PMID:12759351</ref> <ref>PMID:14559997</ref> <ref>PMID:14988723</ref> <ref>PMID:15311285</ref> <ref>PMID:15659650</ref> <ref>PMID:15665856</ref> <ref>PMID:15650047</ref> <ref>PMID:16511572</ref> <ref>PMID:16963448</ref> <ref>PMID:17380128</ref> <ref>PMID:17296736</ref> <ref>PMID:18510930</ref> <ref>PMID:18728393</ref> <ref>PMID:18451105</ref> <ref>PMID:18317453</ref> <ref>PMID:19734889</ref> <ref>PMID:20090422</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Addison, G J.]]	+	[[Category: Addison, G J]]
-	[[Category: Aherne, G W.]]	+	[[Category: Aherne, G W]]
-	[[Category: Allen, C E.]]	+	[[Category: Allen, C E]]
-	[[Category: Boxall, K.]]	+	[[Category: Boxall, K]]
-	[[Category: Cherry, M.]]	+	[[Category: Cherry, M]]
-	[[Category: Collins, I.]]	+	[[Category: Collins, I]]
-	[[Category: Ellard, J.]]	+	[[Category: Ellard, J]]
-	[[Category: Fisher, M.]]	+	[[Category: Fisher, M]]
-	[[Category: Garrett, M D.]]	+	[[Category: Garrett, M D]]
-	[[Category: Klair, S.]]	+	[[Category: Klair, S]]
-	[[Category: Matthews, T P.]]	+	[[Category: Matthews, T P]]
-	[[Category: Mchardy, T.]]	+	[[Category: Mchardy, T]]
-	[[Category: Reader, J C.]]	+	[[Category: Reader, J C]]
-	[[Category: Vanmontfort, R.]]	+	[[Category: Vanmontfort, R]]
-	[[Category: Westwood, I M.]]	+	[[Category: Westwood, I M]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Dna repair]]		[[Category: Dna repair]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 00:56, 2 October 2014

OCA — Thu, 02 Oct 2014 00:56:26 GMT

←Older revision		Revision as of 00:56, 2 October 2014
Line 1:		Line 1:
-	[[~~Image:~~2xez.~~png~~\|~~left~~\|200px]]	+	==CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS==
		+	<StructureSection load='2xez' size='340' side='right' caption='[[2xez]], [[Resolution\|resolution]] 2.25Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2xez]] 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=2XEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XEZ FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XEZ:6-(1H-PYRAZOL-3-YL)-3-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE'>XEZ</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmr\|2wmr]], [[2cgv\|2cgv]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[2cgu\|2cgu]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2bro\|2bro]], [[2c3j\|2c3j]], [[2wmw\|2wmw]], [[2wmu\|2wmu]], [[2brh\|2brh]], [[2x8e\|2x8e]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[2wmq\|2wmq]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[1zys\|1zys]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2x8i\|2x8i]], [[2c3l\|2c3l]], [[2xf0\|2xf0]], [[2xey\|2xey]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xez OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xez RCSB], [http://www.ebi.ac.uk/pdbsum/2xez 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/xe/2xez_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 ==
		+	A range of 3,6-di(hetero)arylimidazo[1,2-a]pyrazine ATP-competitive inhibitors of CHK1 were developed by scaffold hopping from a weakly active screening hit. Efficient synthetic routes for parallel synthesis were developed to prepare analogues with improved potency and ligand efficiency against CHK1. Kinase profiling showed that the imidazo[1,2-a]pyrazines could inhibit other kinases, including CHK2 and ABL, with equivalent or better potency depending on the pendant substitution. These 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines appear to represent a general kinase inhibitor scaffold.

-	~~{{STRUCTURE_2xez\| PDB=2xez \| SCENE= }}~~	+	Design and evaluation of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines as inhibitors of checkpoint and other kinases.,Matthews TP, McHardy T, Klair S, Boxall K, Fisher M, Cherry M, Allen CE, Addison GJ, Ellard J, Aherne GW, Westwood IM, van Montfort R, Garrett MD, Reader JC, Collins I Bioorg Med Chem Lett. 2010 Jul 15;20(14):4045-9. Epub 2010 May 27. PMID:20561787<ref>PMID:20561787</ref>

-	~~===CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20561787}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2xez]] 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=2XEZ OCA].~~	+

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]		*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020561787<~~/~~ref~~><~~ref group="xtra">PMID:019572549</ref><references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 12:58, 20 October 2012

OCA — Sat, 20 Oct 2012 12:58:06 GMT

←Older revision		Revision as of 12:58, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2xez]] is a 1 chain structure ~~of [[Serine/threonine protein kinase]]~~ 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=2XEZ OCA].	+	[[2xez]] 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=2XEZ OCA].

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

OCA at 10:28, 26 July 2012

OCA — Thu, 26 Jul 2012 10:28:52 GMT

←Older revision		Revision as of 10:28, 26 July 2012
Line 1:		Line 1:
	[[Image:2xez.png\|left\|200px]]		[[Image:2xez.png\|left\|200px]]

-	<!--
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-	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.
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	{{STRUCTURE_2xez\| PDB=2xez \| SCENE= }}		{{STRUCTURE_2xez\| PDB=2xez \| SCENE= }}

	===CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS===		===CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20561787}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20561787 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20561787}}		{{ABSTRACT_PUBMED_20561787}}

	==About this Structure==		==About this Structure==
-	[[2xez]] 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=2XEZ OCA].	+	[[2xez]] is a 1 chain structure of [[Serine/threonine protein kinase]] 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=2XEZ OCA].
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20561787~~</ref><ref group="xtra">PMID:~~19572549~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020561787</ref><ref group="xtra">PMID:019572549</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]