2yir - Revision history

OCA at 10:53, 20 December 2023

OCA — Wed, 20 Dec 2023 10:53:23 GMT

←Older revision		Revision as of 10:53, 20 December 2023
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	<StructureSection load='2yir' size='340' side='right'caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2yir' size='340' side='right'caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YIR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YIR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</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]] 2.1Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [https://pdbe.org/2yir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [https://www.ebi.ac.uk/pdbsum/2yir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir 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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [https://pdbe.org/2yir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [https://www.ebi.ac.uk/pdbsum/2yir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:[https://omim.org/entry/609265 609265]]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[https://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500]]. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:12094328</ref> <ref>PMID:21618645</ref>	+	[https://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN] Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:[https://omim.org/entry/609265 609265]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[https://omim.org/entry/176807 176807]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500]. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:12094328</ref> <ref>PMID:21618645</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<ref>PMID:9836640</ref> <ref>PMID:9889122</ref> <ref>PMID:10097108</ref> <ref>PMID:10724175</ref> <ref>PMID:11298456</ref> <ref>PMID:12402044</ref> <ref>PMID:12810724</ref> <ref>PMID:12717439</ref> <ref>PMID:12607004</ref> <ref>PMID:16163388</ref> <ref>PMID:17380128</ref> <ref>PMID:17715138</ref> <ref>PMID:17101782</ref> <ref>PMID:18728393</ref> <ref>PMID:18644861</ref> <ref>PMID:18317453</ref> <ref>PMID:20364141</ref>	+	[https://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<ref>PMID:9836640</ref> <ref>PMID:9889122</ref> <ref>PMID:10097108</ref> <ref>PMID:10724175</ref> <ref>PMID:11298456</ref> <ref>PMID:12402044</ref> <ref>PMID:12810724</ref> <ref>PMID:12717439</ref> <ref>PMID:12607004</ref> <ref>PMID:16163388</ref> <ref>PMID:17380128</ref> <ref>PMID:17715138</ref> <ref>PMID:17101782</ref> <ref>PMID:18728393</ref> <ref>PMID:18644861</ref> <ref>PMID:18317453</ref> <ref>PMID:20364141</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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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: Jobson AG]]
-	[[Category: Jobson~~, A G~~]]	+	[[Category: Lountos GT]]
-	[[Category: Lountos~~, G T~~]]	+	[[Category: Pommier Y]]
-	[[Category: Pommier, Y]]	+	[[Category: Self C]]
-	[[Category: Self, C]]	+	[[Category: Shoemaker RH]]
-	[[Category: Shoemaker~~, R H~~]]	+	[[Category: Tropea JE]]
-	[[Category: Tropea~~, J E~~]]	+	[[Category: Waugh DS]]
-	[[Category: Waugh~~, D S~~]]	+	[[Category: Zhang G]]
-	[[Category: Zhang, G]]	+
-	~~[[Category: Structure-based drug design]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:30, 27 April 2022

OCA — Wed, 27 Apr 2022 12:30:49 GMT

OCA at 12:52, 22 July 2020

OCA — Wed, 22 Jul 2020 12:52:40 GMT

←Older revision		Revision as of 12:52, 22 July 2020
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	==Structural analysis of checkpoint kinase 2 in complex with inhibitor PV1352==		==Structural analysis of checkpoint kinase 2 in complex with inhibitor PV1352==
-	<StructureSection load='2yir' size='340' side='right' caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='2yir' size='340' side='right'caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2YIR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2YIR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [http://pdbe.org/2yir PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [http://www.ebi.ac.uk/pdbsum/2yir PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [http://pdbe.org/2yir PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [http://www.ebi.ac.uk/pdbsum/2yir PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	==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/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Jobson, A G]]		[[Category: Jobson, A G]]

OCA at 09:00, 17 October 2018

OCA — Wed, 17 Oct 2018 09:00:58 GMT

←Older revision		Revision as of 09:00, 17 October 2018
Line 1:		Line 1:

-	==~~STRUCTURAL ANALYSIS OF CHECKPOINT KINASE~~ 2 ~~IN COMPLEX WITH INHIBITOR~~ PV1352==	+	==Structural analysis of checkpoint kinase 2 in complex with inhibitor PV1352==
	<StructureSection load='2yir' size='340' side='right' caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2yir' size='340' side='right' caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 05:36, 5 August 2016

OCA — Fri, 05 Aug 2016 05:36:39 GMT

←Older revision		Revision as of 05:36, 5 August 2016
Line 1:		Line 1:
		+
	==STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352==		==STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352==
	<StructureSection load='2yir' size='340' side='right' caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2yir' size='340' side='right' caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YIR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YIR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [http://www.ebi.ac.uk/pdbsum/2yir 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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [http://pdbe.org/2yir PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [http://www.ebi.ac.uk/pdbsum/2yir PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 2yir" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Jobson, A G]]		[[Category: Jobson, A G]]

OCA at 13:33, 18 December 2014

OCA — Thu, 18 Dec 2014 13:33:46 GMT

←Older revision		Revision as of 13:33, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2yir\| PDB=2yir \| SCENE= }}~~	+	==STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352==
-	===STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352===	+	<StructureSection load='2yir' size='340' side='right' caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21907711}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YIR FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [http://www.ebi.ac.uk/pdbsum/2yir PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:[http://omim.org/entry/609265 609265]]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[http://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:[http://omim.org/entry/259500 259500]]. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:12094328</ref> <ref>PMID:21618645</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<ref>PMID:9836640</ref> <ref>PMID:9889122</ref> <ref>PMID:10097108</ref> <ref>PMID:10724175</ref> <ref>PMID:11298456</ref> <ref>PMID:12402044</ref> <ref>PMID:12810724</ref> <ref>PMID:12717439</ref> <ref>PMID:12607004</ref> <ref>PMID:16163388</ref> <ref>PMID:17380128</ref> <ref>PMID:17715138</ref> <ref>PMID:17101782</ref> <ref>PMID:18728393</ref> <ref>PMID:18644861</ref> <ref>PMID:18317453</ref> <ref>PMID:20364141</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule inhibitors to treat cancer. Here, we report the rational design of Chk2 inhibitors that target the gatekeeper-dependent hydrophobic pocket located behind the adenine-binding region of the ATP-binding site. These compounds exhibit IC(50) values in the low nanomolar range and are highly selective for Chk2 over Chk1. X-ray crystallography was used to determine the structures of the inhibitors in complex with the catalytic kinase domain of Chk2 to verify their modes of binding.

-	~~==Disease==~~	+	X-ray structures of checkpoint kinase 2 in complex with inhibitors that target its gatekeeper-dependent hydrophobic pocket.,Lountos GT, Jobson AG, Tropea JE, Self CR, Zhang G, Pommier Y, Shoemaker RH, Waugh DS FEBS Lett. 2011 Oct 20;585(20):3245-9. Epub 2011 Sep 7. PMID:21907711<ref>PMID:21907711</ref>
-	~~[[http://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Defects in CHEK2 are associated with Li~~-~~Fraumeni syndrome~~ 2 ~~(LFS2) [MIM:[http://omim.org/entry/609265 609265]]; a highly penetrant familial cancer phenotype usually associated~~ with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[http://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that ~~develop in the acini of the prostatic ducts~~. ~~Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma~~, ~~mucinous carcinoma~~, ~~prostatic ductal carcinoma~~, ~~transitional cell carcinoma~~, ~~squamous cell carcinoma~~, ~~basal cell carcinoma~~, ~~adenoid cystic carcinoma (basaloid)~~, ~~signet-ring cell carcinoma and neuroendocrine carcinoma~~. ~~Defects in CHEK2 are found in some patients with osteogenic sarcoma~~ (~~OSRC~~) ~~[MIM~~:~~[http://omim~~.~~org/entry/259500 259500]]~~. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:~~12094328</ref>~~<ref>PMID:~~21618645~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Serine~~/~~threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest~~, ~~activation~~ of ~~DNA repair and apoptosis in response to~~ the ~~presence of DNA double-strand breaks~~. ~~May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-~~S~~/T]~~. ~~Regulates cell cycle checkpoint arrest through phosphorylation~~ of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<~~ref~~>~~PMID:9836640~~</~~ref~~><ref>PMID:9889122</ref><ref>PMID:10097108</ref><ref>PMID:10724175</ref><ref>PMID:11298456</ref><ref>PMID:12402044</ref><ref>PMID:12810724</ref><ref>PMID:12717439</ref><ref>PMID:12607004</ref><ref>PMID:16163388</ref><ref>PMID:17380128</ref><ref>PMID:17715138</ref><ref>PMID:17101782</ref><ref>PMID:18728393</ref><ref>PMID:18644861</ref><ref>PMID:18317453</ref><ref>PMID:20364141</ref>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[2yir]] 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=2YIR 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:021907711</ref><ref group="xtra">PMID:019177354</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Jobson, A G.]]	+	[[Category: Jobson, A G]]
-	[[Category: Lountos, G T.]]	+	[[Category: Lountos, G T]]
-	[[Category: Pommier, Y.]]	+	[[Category: Pommier, Y]]
-	[[Category: Self, C.]]	+	[[Category: Self, C]]
-	[[Category: Shoemaker, R H.]]	+	[[Category: Shoemaker, R H]]
-	[[Category: Tropea, J E.]]	+	[[Category: Tropea, J E]]
-	[[Category: Waugh, D S.]]	+	[[Category: Waugh, D S]]
-	[[Category: Zhang, G.]]	+	[[Category: Zhang, G]]
	[[Category: Structure-based drug design]]		[[Category: Structure-based drug design]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 12:21, 24 March 2013

OCA — Sun, 24 Mar 2013 12:21:01 GMT

←Older revision		Revision as of 12:21, 24 March 2013
Line 1:		Line 1:
-	[[Image:2yir.png\|left\|200px]]
-
	{{STRUCTURE_2yir\| PDB=2yir \| SCENE= }}		{{STRUCTURE_2yir\| PDB=2yir \| SCENE= }}
-
	===STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352===		===STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352===
		+	{{ABSTRACT_PUBMED_21907711}}

-	~~{{ABSTRACT_PUBMED_21907711}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:[http://omim.org/entry/609265 609265]]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[http://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:[http://omim.org/entry/259500 259500]]. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:12094328</ref><ref>PMID:21618645</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<ref>PMID:9836640</ref><ref>PMID:9889122</ref><ref>PMID:10097108</ref><ref>PMID:10724175</ref><ref>PMID:11298456</ref><ref>PMID:12402044</ref><ref>PMID:12810724</ref><ref>PMID:12717439</ref><ref>PMID:12607004</ref><ref>PMID:16163388</ref><ref>PMID:17380128</ref><ref>PMID:17715138</ref><ref>PMID:17101782</ref><ref>PMID:18728393</ref><ref>PMID:18644861</ref><ref>PMID:18317453</ref><ref>PMID:20364141</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021907711</ref><ref group="xtra">PMID:019177354</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021907711</ref><ref group="xtra">PMID:019177354</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 18:45, 20 October 2012

OCA — Sat, 20 Oct 2012 18:45:16 GMT

←Older revision		Revision as of 18:45, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2yir]] 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=2YIR OCA].	+	[[2yir]] 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=2YIR OCA].

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

OCA at 05:07, 27 July 2012

OCA — Fri, 27 Jul 2012 05:07:18 GMT

←Older revision		Revision as of 05:07, 27 July 2012
Line 1:		Line 1:
	[[Image:2yir.png\|left\|200px]]		[[Image:2yir.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2yir", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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	{{STRUCTURE_2yir\| PDB=2yir \| SCENE= }}		{{STRUCTURE_2yir\| PDB=2yir \| SCENE= }}

	===STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352===		===STRUCTURAL ANALYSIS OF CHECKPOINT KINASE 2 IN COMPLEX WITH INHIBITOR PV1352===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21907711}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21907711 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_21907711}}		{{ABSTRACT_PUBMED_21907711}}

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

	==Reference==		==Reference==

OCA at 07:51, 30 October 2011

OCA — Sun, 30 Oct 2011 07:51:21 GMT

←Older revision		Revision as of 07:51, 30 October 2011
Line 1:		Line 1:
-	[[Image:2yir.~~jpg~~\|left\|200px]]	+	[[Image:2yir.png\|left\|200px]]

	<!--		<!--
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	<!--		<!--
-	The line below this paragraph, {{~~ABSTRACT_PUBMED_19177354~~}}, adds the Publication Abstract to the page	+	The line below this paragraph, {{ABSTRACT_PUBMED_21907711}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where ~~19177354~~ is the PubMed ID number.	+	(as it appears on PubMed at http://www.pubmed.gov), where 21907711 is the PubMed ID number.
	-->		-->
-	{{~~ABSTRACT_PUBMED_19177354~~}}	+	{{ABSTRACT_PUBMED_21907711}}

	==About this Structure==		==About this Structure==
-	[[2yir]] 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=2YIR OCA].	+	[[2yir]] 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=2YIR OCA].
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:019177354</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021907711</ref><ref group="xtra">PMID:019177354</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

←Older revision		Revision as of 12:30, 27 April 2022
Line 3:		Line 3:
	<StructureSection load='2yir' size='340' side='right'caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2yir' size='340' side='right'caption='[[2yir]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2YIR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2yir]] 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=2YIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YIR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=YIR:(E)-N-(5-(2-CARBAMIMIDOYLHYDRAZONO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)-7-NITRO-1H-INDOLE-2-CARBOXAMIDE'>YIR</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wti\|2wti]], [[2cn8\|2cn8]], [[2w0j\|2w0j]], [[2ycf\|2ycf]], [[2wtc\|2wtc]], [[2ycr\|2ycr]], [[2ycq\|2ycq]], [[1gxc\|1gxc]], [[2wtd\|2wtd]], [[2xbj\|2xbj]], [[2ycs\|2ycs]], [[2wtj\|2wtj]], [[2xm9\|2xm9]], [[2w7x\|2w7x]], [[2yiq\|2yiq]], [[2cn5\|2cn5]], [[2xm8\|2xm8]], [[2yit\|2yit]]</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~~://proteopedia.org/fgij/fg.htm?mol=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [~~http~~://pdbe.org/2yir PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2yir PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir 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=2yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yir OCA], [https://pdbe.org/2yir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yir RCSB], [https://www.ebi.ac.uk/pdbsum/2yir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yir ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:[~~http~~://omim.org/entry/609265 609265]]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[~~http~~://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:[~~http~~://omim.org/entry/259500 259500]]. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[~~http~~://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:12094328</ref> <ref>PMID:21618645</ref>	+	[[https://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:[https://omim.org/entry/609265 609265]]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.<ref>PMID:11719428</ref> Defects in CHEK2 may be a cause of susceptibility to prostate cancer (PC) [MIM:[https://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in CHEK2 are found in some patients with osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500]]. Defects in CHEK2 is a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=CHEK2 variants are associated with susceptibility to breast cancer and contribute to a substantial fraction of familial breast cancer (PubMed:12094328).<ref>PMID:12094328</ref> <ref>PMID:21618645</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<ref>PMID:9836640</ref> <ref>PMID:9889122</ref> <ref>PMID:10097108</ref> <ref>PMID:10724175</ref> <ref>PMID:11298456</ref> <ref>PMID:12402044</ref> <ref>PMID:12810724</ref> <ref>PMID:12717439</ref> <ref>PMID:12607004</ref> <ref>PMID:16163388</ref> <ref>PMID:17380128</ref> <ref>PMID:17715138</ref> <ref>PMID:17101782</ref> <ref>PMID:18728393</ref> <ref>PMID:18644861</ref> <ref>PMID:18317453</ref> <ref>PMID:20364141</ref>	+	[[https://www.uniprot.org/uniprot/CHK2_HUMAN CHK2_HUMAN]] Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.<ref>PMID:9836640</ref> <ref>PMID:9889122</ref> <ref>PMID:10097108</ref> <ref>PMID:10724175</ref> <ref>PMID:11298456</ref> <ref>PMID:12402044</ref> <ref>PMID:12810724</ref> <ref>PMID:12717439</ref> <ref>PMID:12607004</ref> <ref>PMID:16163388</ref> <ref>PMID:17380128</ref> <ref>PMID:17715138</ref> <ref>PMID:17101782</ref> <ref>PMID:18728393</ref> <ref>PMID:18644861</ref> <ref>PMID:18317453</ref> <ref>PMID:20364141</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==