4rcp - Revision history

OCA at 06:50, 2 March 2023

OCA — Thu, 02 Mar 2023 06:50:01 GMT

←Older revision		Revision as of 06:50, 2 March 2023
Line 3:		Line 3:
	<StructureSection load='4rcp' size='340' side='right'caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4rcp' size='340' side='right'caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rcp]] is a 2 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=4RCP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RCP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rcp]] is a 2 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=4RCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RCP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	~~<tr~~ id~~='NonStdRes'><td class~~="~~sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat~~"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=~~NH2~~:~~AMINO+GROUP~~'>~~NH2~~</scene>, <scene name='pdbligand=~~TPO~~:~~PHOSPHOTHREONINE~~'>~~TPO~~</scene>~~</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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [https://pdbe.org/4rcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [https://www.ebi.ac.uk/pdbsum/4rcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcp ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PLK~~, ~~PLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~<~~/td></tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21]~~ </~~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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [~~http~~://pdbe.org/4rcp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rcp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcp ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PLK1_HUMAN PLK1_HUMAN]] Note=Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.	+	[https://www.uniprot.org/uniprot/PLK1_HUMAN PLK1_HUMAN] Note=Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PLK1_HUMAN PLK1_HUMAN]] Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, MLF1IP, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, PLK1S1/KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGOL1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1 and WEE1. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating PLK1S1/KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, MLF1IP, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, MLF1IP, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGOL1: required for spindle pole localization of isoform 3 of SGOL1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis.<ref>PMID:8991084</ref> <ref>PMID:11202906</ref> <ref>PMID:12207013</ref> <ref>PMID:12447691</ref> <ref>PMID:12852856</ref> <ref>PMID:12738781</ref> <ref>PMID:12939256</ref> <ref>PMID:12524548</ref> <ref>PMID:14734534</ref> <ref>PMID:15469984</ref> <ref>PMID:15070733</ref> <ref>PMID:15148369</ref> <ref>PMID:16198290</ref> <ref>PMID:16980960</ref> <ref>PMID:16247472</ref> <ref>PMID:17081991</ref> <ref>PMID:17617734</ref> <ref>PMID:17376779</ref> <ref>PMID:17351640</ref> <ref>PMID:18418051</ref> <ref>PMID:18521620</ref> <ref>PMID:18331714</ref> <ref>PMID:18477460</ref> <ref>PMID:18174154</ref> <ref>PMID:19160488</ref> <ref>PMID:18615013</ref> <ref>PMID:19473992</ref> <ref>PMID:19509060</ref> <ref>PMID:19351716</ref> <ref>PMID:19468300</ref> <ref>PMID:19468302</ref> <ref>PMID:14532005</ref> <ref>PMID:19597481</ref>	+	[https://www.uniprot.org/uniprot/PLK1_HUMAN PLK1_HUMAN] Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, MLF1IP, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, PLK1S1/KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGOL1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1 and WEE1. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating PLK1S1/KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, MLF1IP, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, MLF1IP, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGOL1: required for spindle pole localization of isoform 3 of SGOL1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis.<ref>PMID:8991084</ref> <ref>PMID:11202906</ref> <ref>PMID:12207013</ref> <ref>PMID:12447691</ref> <ref>PMID:12852856</ref> <ref>PMID:12738781</ref> <ref>PMID:12939256</ref> <ref>PMID:12524548</ref> <ref>PMID:14734534</ref> <ref>PMID:15469984</ref> <ref>PMID:15070733</ref> <ref>PMID:15148369</ref> <ref>PMID:16198290</ref> <ref>PMID:16980960</ref> <ref>PMID:16247472</ref> <ref>PMID:17081991</ref> <ref>PMID:17617734</ref> <ref>PMID:17376779</ref> <ref>PMID:17351640</ref> <ref>PMID:18418051</ref> <ref>PMID:18521620</ref> <ref>PMID:18331714</ref> <ref>PMID:18477460</ref> <ref>PMID:18174154</ref> <ref>PMID:19160488</ref> <ref>PMID:18615013</ref> <ref>PMID:19473992</ref> <ref>PMID:19509060</ref> <ref>PMID:19351716</ref> <ref>PMID:19468300</ref> <ref>PMID:19468302</ref> <ref>PMID:14532005</ref> <ref>PMID:19597481</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==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/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Polo kinase]]~~	+	[[Category: Kim HY]]
-	[[Category: Kim~~, H Y~~]]	+	[[Category: Lee WC]]
-	[[Category: Lee~~, W C~~]]	+	[[Category: Song JH]]
-	[[Category: Song~~, J H]]~~	+
-	~~[[Category: Polo-box domain]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 10:33, 1 May 2019

OCA — Wed, 01 May 2019 10:33:30 GMT

←Older revision		Revision as of 10:33, 1 May 2019
Line 1:		Line 1:

	==Crystal structure of Plk1 Polo-box domain in complex with PL-2==		==Crystal structure of Plk1 Polo-box domain in complex with PL-2==
-	<StructureSection load='4rcp' size='340' side='right' caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4rcp' size='340' side='right'caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rcp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RCP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rcp]] is a 2 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=4RCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RCP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PLK, PLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [http://pdbe.org/4rcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [http://www.ebi.ac.uk/pdbsum/4rcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcp ProSAT]</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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [http://pdbe.org/4rcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [http://www.ebi.ac.uk/pdbsum/4rcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcp ProSAT]</span></td></tr>
Line 29:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Polo kinase]]		[[Category: Polo kinase]]
	[[Category: Kim, H Y]]		[[Category: Kim, H Y]]

OCA at 17:32, 11 August 2016

OCA — Thu, 11 Aug 2016 17:32:25 GMT

←Older revision		Revision as of 17:32, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of Plk1 Polo-box domain in complex with PL-2==		==Crystal structure of Plk1 Polo-box domain in complex with PL-2==
	<StructureSection load='4rcp' size='340' side='right' caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4rcp' size='340' side='right' caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>
Line 6:		Line 7:
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [http://www.ebi.ac.uk/pdbsum/4rcp 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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [http://pdbe.org/4rcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [http://www.ebi.ac.uk/pdbsum/4rcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcp 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 4rcp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:59, 12 November 2014

OCA — Wed, 12 Nov 2014 06:59:01 GMT

←Older revision		Revision as of 06:59, 12 November 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of Plk1 Polo-box domain in complex with PL-2==
		+	<StructureSection load='4rcp' size='340' side='right' caption='[[4rcp]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4rcp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RCP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=56A:3-(8-PHENYLOCTYL)-L-HISTIDINE'>56A</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </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=4rcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rcp RCSB], [http://www.ebi.ac.uk/pdbsum/4rcp PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PLK1_HUMAN PLK1_HUMAN]] Note=Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PLK1_HUMAN PLK1_HUMAN]] Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, MLF1IP, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, PLK1S1/KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGOL1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1 and WEE1. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating PLK1S1/KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, MLF1IP, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, MLF1IP, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGOL1: required for spindle pole localization of isoform 3 of SGOL1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis.<ref>PMID:8991084</ref> <ref>PMID:11202906</ref> <ref>PMID:12207013</ref> <ref>PMID:12447691</ref> <ref>PMID:12852856</ref> <ref>PMID:12738781</ref> <ref>PMID:12939256</ref> <ref>PMID:12524548</ref> <ref>PMID:14734534</ref> <ref>PMID:15469984</ref> <ref>PMID:15070733</ref> <ref>PMID:15148369</ref> <ref>PMID:16198290</ref> <ref>PMID:16980960</ref> <ref>PMID:16247472</ref> <ref>PMID:17081991</ref> <ref>PMID:17617734</ref> <ref>PMID:17376779</ref> <ref>PMID:17351640</ref> <ref>PMID:18418051</ref> <ref>PMID:18521620</ref> <ref>PMID:18331714</ref> <ref>PMID:18477460</ref> <ref>PMID:18174154</ref> <ref>PMID:19160488</ref> <ref>PMID:18615013</ref> <ref>PMID:19473992</ref> <ref>PMID:19509060</ref> <ref>PMID:19351716</ref> <ref>PMID:19468300</ref> <ref>PMID:19468302</ref> <ref>PMID:14532005</ref> <ref>PMID:19597481</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recent progress in the development of peptide-derived Polo-like kinase (Plk1) polo-box domain (PBD) inhibitors has led to the synthesis of multiple peptide ligands with high binding affinity and selectivity. However, few systematic analyses have been conducted to identify key Plk1 residues and characterize their interactions with potent Plk1 peptide inhibitors. We performed systematic deletion analysis using the most potent 4j peptide and studied N-terminal capping of the minimal peptide with diverse organic moieties, leading to the identification of the peptidomimetic 8 (AB-103) series with high binding affinity and selectivity. To evaluate the bioavailability of short peptidomimetic ligands, PEGylated 8 series were synthesized and incubated with HeLa cells to test for cellular uptake, antiproliferative activity, and Plk1 kinase inhibition. Finally, crystallographic studies of the Plk1 PBD in complex with peptidomimetics 8 and 22 (AB-103-5) revealed the presence of two hydrogen bond interactions responsible for their high binding affinity and selectivity.

-	~~The entry 4rcp is ON HOLD until Paper Publication~~	+	A New Class of Peptidomimetics Targeting the Polo-Box Domain of Polo-Like Kinase 1.,Ahn M, Han YH, Park JE, Kim S, Lee WC, Lee SJ, Gunasekaran P, Cheong C, Shin SY Sr, Kim HY, Ryu EK, Murugan RN, Kim NH, Bang JK J Med Chem. 2014 Nov 5. PMID:25347203<ref>PMID:25347203</ref>

-	~~Authors: Lee~~, W.C.~~, Song, J~~.~~H.,~~ Kim, H.Y.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of Plk1~~ Polo-box domain ~~in complex with PL~~-2	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Polo kinase]]
		+	[[Category: Kim, H Y]]
		+	[[Category: Lee, W C]]
		+	[[Category: Song, J H]]
		+	[[Category: Polo-box domain]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:26, 20 October 2014

OCA — Mon, 20 Oct 2014 09:26:01 GMT

←Older revision		Revision as of 09:26, 20 October 2014
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-	The entry 4rcp is ON HOLD	+	The entry 4rcp is ON HOLD until Paper Publication

	Authors: Lee, W.C., Song, J.H., Kim, H.Y.		Authors: Lee, W.C., Song, J.H., Kim, H.Y.

	Description: Crystal structure of Plk1 Polo-box domain in complex with PL-2		Description: Crystal structure of Plk1 Polo-box domain in complex with PL-2

OCA: Protected "4rcp" [edit=sysop:move=sysop]

OCA — Wed, 24 Sep 2014 08:33:30 GMT

Protected "4rcp" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:33, 24 September 2014

OCA: New page: '''Unreleased structure''' The entry 4rcp is ON HOLD Authors: Lee, W.C., Song, J.H., Kim, H.Y. Description: Crystal structure of Plk1 Polo-box domain in complex with PL-2

OCA — Wed, 24 Sep 2014 08:33:28 GMT

New page: '''Unreleased structure''' The entry 4rcp is ON HOLD Authors: Lee, W.C., Song, J.H., Kim, H.Y. Description: Crystal structure of Plk1 Polo-box domain in complex with PL-2

New page

'''Unreleased structure'''

The entry 4rcp is ON HOLD

Authors: Lee, W.C., Song, J.H., Kim, H.Y.

Description: Crystal structure of Plk1 Polo-box domain in complex with PL-2