8bjt - Revision history

OCA at 08:18, 7 February 2024

2024-02-07T08:18:51Z

←Older revision		Revision as of 08:18, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8bjt]] 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=8BJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BJT FirstGlance]. <br>		<table><tr><td colspan='2'>[[8bjt]] 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=8BJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BJT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8X7:1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one'>8X7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.188Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8X7:1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one'>8X7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8bjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bjt OCA], [https://pdbe.org/8bjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bjt RCSB], [https://www.ebi.ac.uk/pdbsum/8bjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bjt 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=8bjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bjt OCA], [https://pdbe.org/8bjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bjt RCSB], [https://www.ebi.ac.uk/pdbsum/8bjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bjt ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[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>		[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>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:03, 26 April 2023

2023-04-26T17:03:57Z

←Older revision		Revision as of 17:03, 26 April 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 8bjt is ON HOLD until Paper Publication~~	+	==Structure of human PLK1 in complex with 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-2-yl]-6-[4-(4-methyl-piperazin-1-yl)-phenylamino]-1,2-dihydro-pyrazolo[3,4-d]pyrimidin-3-one==
-		+	<StructureSection load='8bjt' size='340' side='right'caption='[[8bjt]], [[Resolution\|resolution]] 2.19Å' scene=''>
-	~~Authors: Musil, D., Liu-Bujalski, L.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8bjt]] 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=8BJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BJT FirstGlance]. <br>
-	~~Description:~~ Structure of human PLK1 in complex with 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-2-yl]-6-[4-(4-methyl-piperazin-1-yl)-phenylamino]-1,2-dihydro-pyrazolo[3,4-d]pyrimidin-3-one	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8X7:1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one'>8X7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8bjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bjt OCA], [https://pdbe.org/8bjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bjt RCSB], [https://www.ebi.ac.uk/pdbsum/8bjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bjt ProSAT]</span></td></tr>
-	[[Category: ~~Musil, D~~]]	+	</table>
-	[[Category: Liu-Bujalski, L]]	+	== Disease ==
		+	[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 ==
		+	[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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Liu-Bujalski L]]
		+	[[Category: Musil D]]

OCA at 08:21, 30 November 2022

2022-11-30T08:21:01Z

←Older revision		Revision as of 08:21, 30 November 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8bjt is ON HOLD	+	The entry 8bjt is ON HOLD until Paper Publication

	Authors: Musil, D., Liu-Bujalski, L.		Authors: Musil, D., Liu-Bujalski, L.

OCA: Protected "8bjt" [edit=sysop:move=sysop]

2022-11-16T17:53:49Z

Protected "8bjt" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:53, 16 November 2022

OCA: New page: '''Unreleased structure''' The entry 8bjt is ON HOLD Authors: Musil, D., Liu-Bujalski, L. Description: Structure of human PLK1 in complex with 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-p...

2022-11-16T17:53:48Z

New page: '''Unreleased structure''' The entry 8bjt is ON HOLD Authors: Musil, D., Liu-Bujalski, L. Description: Structure of human PLK1 in complex with 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-p...

New page

'''Unreleased structure'''

The entry 8bjt is ON HOLD

Authors: Musil, D., Liu-Bujalski, L.

Description: Structure of human PLK1 in complex with 2-Allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-pyridin-2-yl]-6-[4-(4-methyl-piperazin-1-yl)-phenylamino]-1,2-dihydro-pyrazolo[3,4-d]pyrimidin-3-one
[[Category: Unreleased Structures]]
[[Category: Musil, D]]
[[Category: Liu-Bujalski, L]]