2wmx - Revision history

OCA at 16:03, 13 December 2023

OCA — Wed, 13 Dec 2023 16:03:14 GMT

←Older revision		Revision as of 16:03, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2wmx' size='340' side='right'caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='2wmx' size='340' side='right'caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2wmx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WMX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WMX FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ZY6:1~~-[~~(2S)-4-(5-PHENYL-1H-PYRAZOLO~~[~~3,4-B~~]~~PYRIDIN-4-YL)MORPHOLIN-~~2~~-YL]METHANAMINE'>ZY6</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]] 2.45Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [https://pdbe.org/2wmx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [https://www.ebi.ac.uk/pdbsum/2wmx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmx 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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [https://pdbe.org/2wmx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [https://www.ebi.ac.uk/pdbsum/2wmx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmx 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: Aherne GW]]
-	[[Category: Aherne~~, G W~~]]	+	[[Category: Boxall K]]
-	[[Category: Boxall, K]]	+	[[Category: Burns S]]
-	[[Category: Burns, S]]	+	[[Category: Cherry M]]
-	[[Category: Cherry, M]]	+	[[Category: Cheung K-MJ]]
-	[[Category: Cheung, K ~~M.J~~]]	+	[[Category: Collins I]]
-	[[Category: Collins, I]]	+	[[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 J]]
-	[[Category: ~~Montfort, R Van~~]]	+	[[Category: Van Montfort R]]
-	[[Category: ~~Reader, J~~]]	+	[[Category: Walton MI]]
-	[[Category: Walton~~, M I~~]]	+	[[Category: Westwood IM]]
-	[[Category: Westwood~~, I M~~]]	+	[[Category: Williams D]]
-	[[Category: Williams, D]]	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Checkpoint kinase]]~~	+
-	~~[[Category: Chk1]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Dna damage]]~~	+
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Isopeptide bond]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Serine/threonine kinase]]~~	+
-	~~[[Category: Serine/threonine-protein kinase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Ubl conjugation~~]]	+

OCA at 10:56, 7 July 2021

OCA — Wed, 07 Jul 2021 10:56:31 GMT

←Older revision		Revision as of 10:56, 7 July 2021
Line 3:		Line 3:
	<StructureSection load='2wmx' size='340' side='right'caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='2wmx' size='340' side='right'caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2wmx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2WMX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2wmx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WMX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [~~http~~://pdbe.org/2wmx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2wmx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmx 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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [https://pdbe.org/2wmx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [https://www.ebi.ac.uk/pdbsum/2wmx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmx 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 06:56, 7 August 2019

OCA — Wed, 07 Aug 2019 06:56:57 GMT

←Older revision		Revision as of 06:56, 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='2wmx' size='340' side='right' caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>	+	<StructureSection load='2wmx' size='340' side='right'caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2wmx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>		<table><tr><td colspan='2'>[[2wmx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX 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/wm/2wmx_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wm/2wmx_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 2wmx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2wmx" 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: Aherne, G W]]		[[Category: Aherne, G W]]

OCA at 12:03, 6 November 2017

OCA — Mon, 06 Nov 2017 12:03:16 GMT

←Older revision		Revision as of 12:03, 6 November 2017
Line 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 2wmx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2wmx" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:55, 3 August 2017

OCA — Thu, 03 Aug 2017 10:55:31 GMT

←Older revision		Revision as of 10:55, 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='2wmx' size='340' side='right' caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='2wmx' size='340' side='right' caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2wmx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://pdbe.org/2wmx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx 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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://pdbe.org/2wmx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Aherne, G W]]		[[Category: Aherne, G W]]
Line 48:		Line 48:
	[[Category: Klair, S]]		[[Category: Klair, S]]
	[[Category: Matthews, T P]]		[[Category: Matthews, T P]]
-	[[Category: ~~Mchardy~~, T]]	+	[[Category: McHardy, T]]
	[[Category: Montfort, R Van]]		[[Category: Montfort, R Van]]
	[[Category: Reader, J]]		[[Category: Reader, J]]
Line 58:		Line 58:
	[[Category: Checkpoint kinase]]		[[Category: Checkpoint kinase]]
	[[Category: Chk1]]		[[Category: Chk1]]
		+	[[Category: Cytoplasm]]
	[[Category: Dna damage]]		[[Category: Dna damage]]
	[[Category: Dna repair]]		[[Category: Dna repair]]
Line 65:		Line 66:
	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
		+	[[Category: Polymorphism]]
	[[Category: Serine/threonine kinase]]		[[Category: Serine/threonine kinase]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]
		+	[[Category: Ubl conjugation]]

OCA at 15:08, 9 February 2016

OCA — Tue, 09 Feb 2016 15:08:11 GMT

←Older revision		Revision as of 15:08, 9 February 2016
Line 2:		Line 2:
	<StructureSection load='2wmx' size='340' side='right' caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='2wmx' size='340' side='right' caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx 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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://pdbe.org/2wmx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 18:
	<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=2wmx ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		Line 28:
	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 2wmx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Aherne, G W]]		[[Category: Aherne, G W]]

OCA at 07:36, 25 December 2014

OCA — Thu, 25 Dec 2014 07:36:10 GMT

←Older revision		Revision as of 07:36, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>		<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx 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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx 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: Aherne, G W.]]	+	[[Category: Aherne, G W]]
-	[[Category: Boxall, K.]]	+	[[Category: Boxall, K]]
-	[[Category: Burns, S.]]	+	[[Category: Burns, S]]
-	[[Category: Cherry, M.]]	+	[[Category: Cherry, M]]
-	[[Category: Cheung, K M.J.]]	+	[[Category: Cheung, K M.J]]
-	[[Category: Collins, I.]]	+	[[Category: Collins, I]]
-	[[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: Montfort, R Van.]]	+	[[Category: Montfort, R Van]]
-	[[Category: Reader, J.]]	+	[[Category: Reader, J]]
-	[[Category: Walton, M I.]]	+	[[Category: Walton, M I]]
-	[[Category: Westwood, I M.]]	+	[[Category: Westwood, I M]]
-	[[Category: Williams, D.]]	+	[[Category: Williams, D]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]

OCA at 07:46, 29 September 2014

OCA — Mon, 29 Sep 2014 07:46:40 GMT

←Older revision		Revision as of 07:46, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~2wmx.~~png~~\|~~left~~\|200px]]	+	==CRYSTAL STRUCTURE OF CHECKPOINT KINASE 1 (CHK1) IN COMPLEX WITH INHIBITORS==
		+	<StructureSection load='2wmx' size='340' side='right' caption='[[2wmx]], [[Resolution\|resolution]] 2.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2wmx]] 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=2WMX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMX FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY6:1-[(2S)-4-(5-PHENYL-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE'>ZY6</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2brh\|2brh]], [[2cgv\|2cgv]], [[2c3k\|2c3k]], [[1nvr\|1nvr]], [[1zlt\|1zlt]], [[2cgw\|2cgw]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[1ia8\|1ia8]], [[2br1\|2br1]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2c3l\|2c3l]], [[2wmq\|2wmq]], [[2wmr\|2wmr]], [[2wmt\|2wmt]], [[2wmu\|2wmu]], [[2wmv\|2wmv]], [[2wmw\|2wmw]]</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=2wmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmx RCSB], [http://www.ebi.ac.uk/pdbsum/2wmx 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/wm/2wmx_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 ==
		+	Checkpoint kinase 1 (CHK1) is an oncology target of significant current interest. Inhibition of CHK1 abrogates DNA damage-induced cell cycle checkpoints and sensitizes p53 deficient cancer cells to genotoxic therapies. Using template screening, a fragment-based approach to small molecule hit generation, we have identified multiple CHK1 inhibitor scaffolds suitable for further optimization. The sequential combination of in silico low molecular weight template selection, a high concentration biochemical assay and hit validation through protein-ligand X-ray crystallography provided 13 template hits from an initial in silico screening library of ca. 15000 compounds. The use of appropriate counter-screening to rule out nonspecific aggregation by test compounds was essential for optimum performance of the high concentration bioassay. One low molecular weight, weakly active purine template hit was progressed by iterative structure-based design to give submicromolar pyrazolopyridines with good ligand efficiency and appropriate CHK1-mediated cellular activity in HT29 colon cancer cells.

-	~~{{STRUCTURE_2wmx\| PDB=2wmx \| SCENE= }}~~	+	Identification of inhibitors of checkpoint kinase 1 through template screening.,Matthews TP, Klair S, Burns S, Boxall K, Cherry M, Fisher M, Westwood IM, Walton MI, McHardy T, Cheung KM, Van Montfort R, Williams D, Aherne GW, Garrett MD, Reader J, Collins I J Med Chem. 2009 Aug 13;52(15):4810-9. PMID:19572549<ref>PMID:19572549</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_19572549}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2wmx]] 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=2WMX 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: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 14:15, 20 October 2012

OCA — Sat, 20 Oct 2012 14:15:32 GMT

←Older revision		Revision as of 14:15, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2wmx]] 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=2WMX OCA].	+	[[2wmx]] 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=2WMX OCA].

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

OCA at 14:33, 26 July 2012

OCA — Thu, 26 Jul 2012 14:33:45 GMT

←Older revision		Revision as of 14:33, 26 July 2012
Line 1:		Line 1:
	[[Image:2wmx.png\|left\|200px]]		[[Image:2wmx.png\|left\|200px]]

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	{{STRUCTURE_2wmx\| PDB=2wmx \| SCENE= }}		{{STRUCTURE_2wmx\| PDB=2wmx \| SCENE= }}

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

-
-	<!--
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	==See Also==		==See Also==
-	*[[Serine/threonine protein kinase]]	+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]

	==Reference==		==Reference==