2x8i - Revision history

OCA at 10:26, 20 December 2023

2023-12-20T10:26:27Z

←Older revision		Revision as of 10:26, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='2x8i' size='340' side='right'caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='2x8i' size='340' side='right'caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2x8i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X8I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.92Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [https://pdbe.org/2x8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [https://www.ebi.ac.uk/pdbsum/2x8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8i 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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [https://pdbe.org/2x8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [https://www.ebi.ac.uk/pdbsum/2x8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8i 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: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Breed J]]
-	[[Category: Breed, J]]	+	[[Category: Haye H]]
-	[[Category: Haye, H]]	+	[[Category: McCall E]]
-	[[Category: McCall, E]]	+	[[Category: Otterbein L]]
-	[[Category: Otterbein, L]]	+	[[Category: Read JA]]
-	[[Category: Read~~, J A~~]]	+	[[Category: Vallentine A]]
-	[[Category: Vallentine, A]]	+	[[Category: White A]]
-	[[Category: White, A]]	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Cytoskeleton]]~~	+
-	~~[[Category: Dna damage]]~~	+
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Isopeptide bond]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:36, 10 November 2021

2021-11-10T08:36:59Z

←Older revision		Revision as of 08:36, 10 November 2021
Line 3:		Line 3:
	<StructureSection load='2x8i' size='340' side='right'caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='2x8i' size='340' side='right'caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2X8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2x8i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X8I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [~~http~~://pdbe.org/2x8i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2x8i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8i 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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [https://pdbe.org/2x8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [https://www.ebi.ac.uk/pdbsum/2x8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8i 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 12:22, 10 May 2019

2019-05-10T12:22:59Z

←Older revision		Revision as of 12:22, 10 May 2019
Line 1:		Line 1:

	==Discovery of a Novel Class of triazolones as Checkpoint Kinase Inhibitors - Hit to Lead Exploration==		==Discovery of a Novel Class of triazolones as Checkpoint Kinase Inhibitors - Hit to Lead Exploration==
-	<StructureSection load='2x8i' size='340' side='right' caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>	+	<StructureSection load='2x8i' size='340' side='right'caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>		<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Breed, J]]		[[Category: Breed, J]]

OCA at 09:53, 3 October 2018

2018-10-03T09:53:32Z

←Older revision		Revision as of 09:53, 3 October 2018
Line 1:		Line 1:

-	==~~DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS~~ - ~~HIT TO LEAD EXPLORATION~~==	+	==Discovery of a Novel Class of triazolones as Checkpoint Kinase Inhibitors - Hit to Lead Exploration==
	<StructureSection load='2x8i' size='340' side='right' caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='2x8i' size='340' side='right' caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
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/x8/2x8i_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x8/2x8i_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 41:		Line 41:
	[[Category: Breed, J]]		[[Category: Breed, J]]
	[[Category: Haye, H]]		[[Category: Haye, H]]
-	[[Category: ~~Mccall~~, E]]	+	[[Category: McCall, E]]
	[[Category: Otterbein, L]]		[[Category: Otterbein, L]]
	[[Category: Read, J A]]		[[Category: Read, J A]]

OCA at 17:53, 4 August 2016

2016-08-04T17:53:55Z

←Older revision		Revision as of 17:53, 4 August 2016
Line 1:		Line 1:
		+
	==DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS - HIT TO LEAD EXPLORATION==		==DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS - HIT TO LEAD EXPLORATION==
	<StructureSection load='2x8i' size='340' side='right' caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='2x8i' size='340' side='right' caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [http://www.ebi.ac.uk/pdbsum/2x8i 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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [http://pdbe.org/2x8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [http://www.ebi.ac.uk/pdbsum/2x8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8i 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=2x8i 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 2x8i" 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: Breed, J]]		[[Category: Breed, J]]

OCA at 11:38, 25 December 2014

2014-12-25T11:38:00Z

←Older revision		Revision as of 11:38, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>		<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [http://www.ebi.ac.uk/pdbsum/2x8i 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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [http://www.ebi.ac.uk/pdbsum/2x8i 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: Breed, J.]]	+	[[Category: Breed, J]]
-	[[Category: Haye, H.]]	+	[[Category: Haye, H]]
-	[[Category: Mccall, E.]]	+	[[Category: Mccall, E]]
-	[[Category: Otterbein, L.]]	+	[[Category: Otterbein, L]]
-	[[Category: Read, J A.]]	+	[[Category: Read, J A]]
-	[[Category: Vallentine, A.]]	+	[[Category: Vallentine, A]]
-	[[Category: White, A.]]	+	[[Category: White, A]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Cytoskeleton]]		[[Category: Cytoskeleton]]

OCA at 01:05, 2 October 2014

2014-10-02T01:05:24Z

←Older revision		Revision as of 01:05, 2 October 2014
Line 1:		Line 1:
-	[[~~Image:~~2x8i.~~png~~\|~~left~~\|200px]]	+	==DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS - HIT TO LEAD EXPLORATION==
		+	<StructureSection load='2x8i' size='340' side='right' caption='[[2x8i]], [[Resolution\|resolution]] 1.92Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2x8i]] 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=2X8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8I FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8I:7-(3-HYDROXYPHENYL)-5-METHYL[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>X8I</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wmt\|2wmt]], [[2cgx\|2cgx]], [[2c3j\|2c3j]], [[2bro\|2bro]], [[2brb\|2brb]], [[2x8d\|2x8d]], [[2wmw\|2wmw]], [[2wmr\|2wmr]], [[2wmu\|2wmu]], [[2x8e\|2x8e]], [[2cgv\|2cgv]], [[2brh\|2brh]], [[1nvr\|1nvr]], [[2c3k\|2c3k]], [[2wmq\|2wmq]], [[2cgw\|2cgw]], [[1zlt\|1zlt]], [[2brn\|2brn]], [[2ayp\|2ayp]], [[2wmx\|2wmx]], [[1zys\|1zys]], [[2cgu\|2cgu]], [[2br1\|2br1]], [[1ia8\|1ia8]], [[2brg\|2brg]], [[1nvs\|1nvs]], [[2brm\|2brm]], [[1nvq\|1nvq]], [[2wms\|2wms]], [[2wmv\|2wmv]], [[2c3l\|2c3l]]</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=2x8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x8i RCSB], [http://www.ebi.ac.uk/pdbsum/2x8i 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/x8/2x8i_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, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described.

-	~~{{STRUCTURE_2x8i\| PDB=2x8i \| SCENE= }}~~	+	Discovery of a novel class of triazolones as Checkpoint Kinase inhibitors--hit to lead exploration.,Oza V, Ashwell S, Brassil P, Breed J, Deng C, Ezhuthachan J, Haye H, Horn C, Janetka J, Lyne P, Newcombe N, Otterbien L, Pass M, Read J, Roswell S, Su M, Toader D, Yu D, Yu Y, Valentine A, Webborn P, White A, Zabludoff S, Zheng X Bioorg Med Chem Lett. 2010 Sep 1;20(17):5133-8. Epub 2010 Jul 29. PMID:20673630<ref>PMID:20673630</ref>

-	~~===DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS - HIT TO LEAD EXPLORATION===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20673630}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2x8i]] 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=2X8I 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:020673630<~~/~~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 16:15, 20 October 2012

2012-10-20T16:15:06Z

←Older revision		Revision as of 16:15, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2x8i]] 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=2X8I OCA].	+	[[2x8i]] 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=2X8I OCA].

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

OCA: Protected "2x8i" [edit=sysop:move=sysop]

2012-07-26T21:04:35Z

Protected "2x8i" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:04, 26 July 2012

OCA at 21:04, 26 July 2012

2012-07-26T21:04:34Z

←Older revision		Revision as of 21:04, 26 July 2012
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-	{{Seed}}
	[[Image:2x8i.png\|left\|200px]]		[[Image:2x8i.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_2x8i\| PDB=2x8i \| SCENE= }}		{{STRUCTURE_2x8i\| PDB=2x8i \| SCENE= }}

	===DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS - HIT TO LEAD EXPLORATION===		===DISCOVERY OF A NOVEL CLASS OF TRIAZOLONES AS CHECKPOINT KINASE INHIBITORS - HIT TO LEAD EXPLORATION===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20673630}}, adds the Publication Abstract to the page
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	{{ABSTRACT_PUBMED_20673630}}		{{ABSTRACT_PUBMED_20673630}}

	==About this Structure==		==About this Structure==
-	~~2X8I~~ 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=2X8I OCA].	+	[[2x8i]] 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=2X8I OCA].
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20673630~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020673630</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
Line 41:		Line 32:
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	[[Category: Transferase]]		[[Category: Transferase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 25 08:27:25 2010''