4o6w - Revision history

OCA at 08:58, 18 January 2023

OCA — Wed, 18 Jan 2023 08:58:34 GMT

←Older revision		Revision as of 08:58, 18 January 2023
Line 3:		Line 3:
	<StructureSection load='4o6w' size='340' side='right'caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='4o6w' size='340' side='right'caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4o6w]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mlu 4mlu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4O6W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4o6w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mlu 4mlu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O6W FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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">PLK1, PLK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [https://pdbe.org/4o6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [https://www.ebi.ac.uk/pdbsum/4o6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6w ProSAT]</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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [~~http~~://pdbe.org/4o6w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4o6w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6w 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 24:		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: Burke TR]]
-	[[Category: Burke~~, T R~~]]	+	[[Category: Lee K-W]]
-	[[Category: Lee, K S]]	+	[[Category: Lee KS]]
-	[[Category: Lee~~, K W~~]]	+	[[Category: Lim DC]]
-	[[Category: Lim~~, D C~~]]	+	[[Category: Park J-E]]
-	[[Category: Park, J E]]	+	[[Category: Park S-Y]]
-	[[Category: Park, S Y]]	+	[[Category: Qian W-J]]
-	[[Category: Qian, W J]]	+	[[Category: Yaffe MB]]
-	[[Category: Yaffe~~, M B]]~~	+
-	~~[[Category: Phospho-peptide binding]]~~	+
-	~~[[Category: Phosphopeptide]]~~	+
-	~~[[Category: Polo box domain]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:48, 10 April 2019

OCA — Wed, 10 Apr 2019 08:48:05 GMT

←Older revision		Revision as of 08:48, 10 April 2019
Line 1:		Line 1:

	==Peptide-Based Inhibitors of Plk1 Polo-box Domain==		==Peptide-Based Inhibitors of Plk1 Polo-box Domain==
-	<StructureSection load='4o6w' size='340' side='right' caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='4o6w' size='340' side='right'caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4o6w]] is a 2 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mlu 4mlu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O6W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4o6w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mlu 4mlu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O6W FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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">PLK1, PLK ([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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [http://pdbe.org/4o6w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [http://www.ebi.ac.uk/pdbsum/4o6w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6w 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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [http://pdbe.org/4o6w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [http://www.ebi.ac.uk/pdbsum/4o6w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6w ProSAT]</span></td></tr>
Line 28:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Polo kinase]]		[[Category: Polo kinase]]
	[[Category: Burke, T R]]		[[Category: Burke, T R]]

OCA at 16:55, 2 January 2017

OCA — Mon, 02 Jan 2017 16:55:49 GMT

←Older revision		Revision as of 16:55, 2 January 2017
Line 1:		Line 1:
		+
	==Peptide-Based Inhibitors of Plk1 Polo-box Domain==		==Peptide-Based Inhibitors of Plk1 Polo-box Domain==
	<StructureSection load='4o6w' size='340' side='right' caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='4o6w' size='340' side='right' caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [http://www.ebi.ac.uk/pdbsum/4o6w 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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [http://pdbe.org/4o6w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [http://www.ebi.ac.uk/pdbsum/4o6w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6w ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4o6w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:27, 3 December 2014

OCA — Wed, 03 Dec 2014 09:27:43 GMT

←Older revision		Revision as of 09:27, 3 December 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Peptide-Based Inhibitors of Plk1 Polo-box Domain==
		+	<StructureSection load='4o6w' size='340' side='right' caption='[[4o6w]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4o6w]] is a 2 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mlu 4mlu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O6W FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2SO:3-{3-[(3R)-3,4-DIHYDROXYBUTYL]-1-(8-PHENYLOCTYL)-1H-IMIDAZOL-3-IUM-5-YL}-L-ALANINE'>2SO</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=4o6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o6w RCSB], [http://www.ebi.ac.uk/pdbsum/4o6w 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 ==
		+	Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(tau)-alkylation of histidine residues already bearing a N(pi)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics. (c) 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 444-455, 2014.

-	~~The entry 4o6w is ON HOLD until Paper Publication~~	+	Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in hela cells.,Qian WJ, Park JE, Lim D, Lai CC, Kelley JA, Park SY, Lee KW, Yaffe MB, Lee KS, Burke TR Jr Biopolymers. 2014 Nov;102(6):444-55. doi: 10.1002/bip.22569. PMID:25283071<ref>PMID:25283071</ref>

-	~~Authors: Qian~~, W.-J., ~~Park~~, ~~J.-E.~~, Lim, D.C., Park, S.-Y~~., Lee~~, ~~K.-~~W., Yaffe, M.B~~., Lee, K.S., Burke, T.R.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Peptide~~-~~Based Inhibitors of Plk1~~ Polo-box ~~Domain~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Polo kinase]]
		+	[[Category: Burke, T R]]
		+	[[Category: Lee, K S]]
		+	[[Category: Lee, K W]]
		+	[[Category: Lim, D C]]
		+	[[Category: Park, J E]]
		+	[[Category: Park, S Y]]
		+	[[Category: Qian, W J]]
		+	[[Category: Yaffe, M B]]
		+	[[Category: Phospho-peptide binding]]
		+	[[Category: Phosphopeptide]]
		+	[[Category: Polo box domain]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 08:43, 26 March 2014

OCA — Wed, 26 Mar 2014 08:43:19 GMT

←Older revision		Revision as of 08:43, 26 March 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4o6w is ON HOLD	+	The entry 4o6w is ON HOLD until Paper Publication

	Authors: Qian, W.-J., Park, J.-E., Lim, D.C., Park, S.-Y., Lee, K.-W., Yaffe, M.B., Lee, K.S., Burke, T.R.		Authors: Qian, W.-J., Park, J.-E., Lim, D.C., Park, S.-Y., Lee, K.-W., Yaffe, M.B., Lee, K.S., Burke, T.R.

	Description: Peptide-Based Inhibitors of Plk1 Polo-box Domain		Description: Peptide-Based Inhibitors of Plk1 Polo-box Domain

OCA at 07:04, 29 January 2014

OCA — Wed, 29 Jan 2014 07:04:33 GMT

←Older revision		Revision as of 07:04, 29 January 2014
Line 3:		Line 3:
	The entry 4o6w is ON HOLD		The entry 4o6w is ON HOLD

-	Authors: Qian, W-J, Park, J-E, Lim, D.C., Park, S-Y, Lee, K-W, Yaffe, M.B., Lee, K.S., Burke, T.R.	+	Authors: Qian, W.-J., Park, J.-E., Lim, D.C., Park, S.-Y., Lee, K.-W., Yaffe, M.B., Lee, K.S., Burke, T.R.

	Description: Peptide-Based Inhibitors of Plk1 Polo-box Domain		Description: Peptide-Based Inhibitors of Plk1 Polo-box Domain

OCA: Protected "4o6w" [edit=sysop:move=sysop]

OCA — Wed, 08 Jan 2014 09:25:19 GMT

Protected "4o6w" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:25, 8 January 2014

OCA: New page: '''Unreleased structure''' The entry 4o6w is ON HOLD Authors: Qian, W-J, Park, J-E, Lim, D.C., Park, S-Y, Lee, K-W, Yaffe, M.B., Lee, K.S., Burke, T.R. Description: Peptide-Based Inhib...

OCA — Wed, 08 Jan 2014 09:25:17 GMT

New page: '''Unreleased structure''' The entry 4o6w is ON HOLD Authors: Qian, W-J, Park, J-E, Lim, D.C., Park, S-Y, Lee, K-W, Yaffe, M.B., Lee, K.S., Burke, T.R. Description: Peptide-Based Inhib...

New page

'''Unreleased structure'''

The entry 4o6w is ON HOLD

Authors: Qian, W-J, Park, J-E, Lim, D.C., Park, S-Y, Lee, K-W, Yaffe, M.B., Lee, K.S., Burke, T.R.

Description: Peptide-Based Inhibitors of Plk1 Polo-box Domain