7dho - Revision history

OCA at 16:33, 29 November 2023

OCA — Wed, 29 Nov 2023 16:33:37 GMT

←Older revision		Revision as of 16:33, 29 November 2023
Line 3:		Line 3:
	<StructureSection load='7dho' size='340' side='right'caption='[[7dho]], [[Resolution\|resolution]] 3.29Å' scene=''>		<StructureSection load='7dho' size='340' side='right'caption='[[7dho]], [[Resolution\|resolution]] 3.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7dho]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7dho]] 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=7DHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHO FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=H7U:2~~-~~methoxy-9-(piperidin-4-ylmethylsulfanyl)-7-propan-2-yloxy-acridine'>H7U</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]] 3.29Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~PTR~~:O-~~PHOSPHOTYROSINE~~'>~~PTR~~</scene>, <scene name='pdbligand=~~SEP~~:~~PHOSPHOSERINE~~'>~~SEP~~</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H7U:2-methoxy-9-(piperidin-4-ylmethylsulfanyl)-7-propan-2-yloxy-acridine'>H7U</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1]~~ </~~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=7dho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dho OCA], [https://pdbe.org/7dho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dho RCSB], [https://www.ebi.ac.uk/pdbsum/7dho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dho 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=7dho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dho OCA], [https://pdbe.org/7dho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dho RCSB], [https://www.ebi.ac.uk/pdbsum/7dho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dho ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/DYRK2_HUMAN DYRK2_HUMAN]] Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro).<ref>PMID:9748265</ref> <ref>PMID:11311121</ref> <ref>PMID:12588975</ref> <ref>PMID:14593110</ref> <ref>PMID:15910284</ref> <ref>PMID:16611631</ref> <ref>PMID:16511445</ref> <ref>PMID:17349958</ref> <ref>PMID:18599021</ref> <ref>PMID:18455992</ref> <ref>PMID:19287380</ref> <ref>PMID:22307329</ref> <ref>PMID:22878263</ref>	+	[https://www.uniprot.org/uniprot/DYRK2_HUMAN DYRK2_HUMAN] Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro).<ref>PMID:9748265</ref> <ref>PMID:11311121</ref> <ref>PMID:12588975</ref> <ref>PMID:14593110</ref> <ref>PMID:15910284</ref> <ref>PMID:16611631</ref> <ref>PMID:16511445</ref> <ref>PMID:17349958</ref> <ref>PMID:18599021</ref> <ref>PMID:18455992</ref> <ref>PMID:19287380</ref> <ref>PMID:22307329</ref> <ref>PMID:22878263</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dual-specificity kinase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Wei, T]]	+	[[Category: Wei T]]
-	[[Category: Xiao, J]]	+	[[Category: Xiao J]]
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase~~]]	+

OCA at 05:34, 8 June 2022

OCA — Wed, 08 Jun 2022 05:34:06 GMT

←Older revision		Revision as of 05:34, 8 June 2022
Line 1:		Line 1:

	==The co-crystal structure of DYRK2 with a small molecule inhibitor 14==		==The co-crystal structure of DYRK2 with a small molecule inhibitor 14==
-	<StructureSection load='7dho' size='340' side='right'caption='[[7dho]]' scene=''>	+	<StructureSection load='7dho' size='340' side='right'caption='[[7dho]], [[Resolution\|resolution]] 3.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7dho]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHO FirstGlance]. <br>
-	</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=7dho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dho OCA], [https://pdbe.org/7dho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dho RCSB], [https://www.ebi.ac.uk/pdbsum/7dho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dho ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H7U:2-methoxy-9-(piperidin-4-ylmethylsulfanyl)-7-propan-2-yloxy-acridine'>H7U</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </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=7dho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dho OCA], [https://pdbe.org/7dho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dho RCSB], [https://www.ebi.ac.uk/pdbsum/7dho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dho ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/DYRK2_HUMAN DYRK2_HUMAN]] Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro).<ref>PMID:9748265</ref> <ref>PMID:11311121</ref> <ref>PMID:12588975</ref> <ref>PMID:14593110</ref> <ref>PMID:15910284</ref> <ref>PMID:16611631</ref> <ref>PMID:16511445</ref> <ref>PMID:17349958</ref> <ref>PMID:18599021</ref> <ref>PMID:18455992</ref> <ref>PMID:19287380</ref> <ref>PMID:22307329</ref> <ref>PMID:22878263</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The dual-specificity tyrosine phosphorylation-regulated kinase DYRK2 has emerged as a critical regulator of cellular processes. We took a chemical biology approach to gain further insights into its function. We developed C17, a potent small-molecule DYRK2 inhibitor, through multiple rounds of structure-based optimization guided by several co-crystallized structures. C17 displayed an effect on DYRK2 at a single-digit nanomolar IC50 and showed outstanding selectivity for the human kinome containing 467 other human kinases. Using C17 as a chemical probe, we further performed quantitative phosphoproteomic assays and identified several novel DYRK2 targets, including eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and stromal interaction molecule 1 (STIM1). DYRK2 phosphorylated 4E-BP1 at multiple sites, and the combined treatment of C17 with AKT and MEK inhibitors showed synergistic 4E-BP1 phosphorylation suppression. The phosphorylation of STIM1 by DYRK2 substantially increased the interaction of STIM1 with the ORAI1 channel, and C17 impeded the store-operated calcium entry process. These studies collectively further expand our understanding of DYRK2 and provide a valuable tool to pinpoint its biological function.
		+
		+	Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry.,Wei T, Wang J, Liang R, Chen W, Chen Y, Ma M, He A, Du Y, Zhou W, Zhang Z, Zeng X, Wang C, Lu J, Guo X, Chen XW, Wang Y, Tian R, Xiao J, Lei X Elife. 2022 Apr 19;11. pii: 77696. doi: 10.7554/eLife.77696. PMID:35439114<ref>PMID:35439114</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7dho" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Dual-specificity kinase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Wei T]]	+	[[Category: Wei, T]]
-	[[Category: Xiao J]]	+	[[Category: Xiao, J]]
		+	[[Category: Cell cycle]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]

OCA at 13:35, 17 November 2021

OCA — Wed, 17 Nov 2021 13:35:30 GMT

←Older revision		Revision as of 13:35, 17 November 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 7dho ~~is ON HOLD until Paper Publication~~	+	==The co-crystal structure of DYRK2 with a small molecule inhibitor 14==
-		+	<StructureSection load='7dho' size='340' side='right'caption='[[7dho]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHO FirstGlance]. <br>
-	~~Description~~:	+	</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=7dho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dho OCA], [https://pdbe.org/7dho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dho RCSB], [https://www.ebi.ac.uk/pdbsum/7dho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dho ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Wei T]]
		+	[[Category: Xiao J]]

OCA at 08:38, 19 May 2021

OCA — Wed, 19 May 2021 08:38:19 GMT

←Older revision		Revision as of 08:38, 19 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7dho is ON HOLD	+	The entry 7dho is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7dho" [edit=sysop:move=sysop]

OCA — Wed, 25 Nov 2020 05:23:31 GMT

Protected "7dho" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:23, 25 November 2020

OCA: New page: '''Unreleased structure''' The entry 7dho is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 25 Nov 2020 05:23:30 GMT

New page: '''Unreleased structure''' The entry 7dho is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7dho is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]