5xvg - Revision history

OCA at 08:15, 22 November 2023

OCA — Wed, 22 Nov 2023 08:15:03 GMT

←Older revision		Revision as of 08:15, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5xvg' size='340' side='right'caption='[[5xvg]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='5xvg' size='340' side='right'caption='[[5xvg]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xvg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5XVG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xvg]] 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=5XVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XVG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8FX:[6-chloranyl-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]-[(3R)-3-methylpiperazin-1-yl]methanone'>8FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.1Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<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=8FX:[6-chloranyl-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]-[(3R)-3-methylpiperazin-1-yl]methanone'>8FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xvg OCA], [https://pdbe.org/5xvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xvg RCSB], [https://www.ebi.ac.uk/pdbsum/5xvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xvg ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5xvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xvg OCA], [~~http~~://pdbe.org/5xvg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xvg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xvg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xvg ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PAK4_HUMAN PAK4_HUMAN]] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.<ref>PMID:11278822</ref> <ref>PMID:11313478</ref> <ref>PMID:14560027</ref> <ref>PMID:15660133</ref> <ref>PMID:20507994</ref> <ref>PMID:20805321</ref> <ref>PMID:20631255</ref>	+	[https://www.uniprot.org/uniprot/PAK4_HUMAN PAK4_HUMAN] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.<ref>PMID:11278822</ref> <ref>PMID:11313478</ref> <ref>PMID:14560027</ref> <ref>PMID:15660133</ref> <ref>PMID:20507994</ref> <ref>PMID:20805321</ref> <ref>PMID:20631255</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Li H]]
-	[[Category: Li, H]]	+	[[Category: Zhao F]]
-	[[Category: Zhao, F]]	+
-	~~[[Category: Atp binding pocket]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:59, 14 October 2020

OCA — Wed, 14 Oct 2020 06:59:33 GMT

←Older revision		Revision as of 06:59, 14 October 2020
Line 1:		Line 1:

	==Crystal Structure of PAK4 in complex with inhibitor CZH226==		==Crystal Structure of PAK4 in complex with inhibitor CZH226==
-	<StructureSection load='5xvg' size='340' side='right' caption='[[5xvg]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='5xvg' size='340' side='right'caption='[[5xvg]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xvg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVG OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XVG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xvg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XVG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8FX:[6-chloranyl-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]-[(3R)-3-methylpiperazin-1-yl]methanone'>8FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8FX:[6-chloranyl-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]-[(3R)-3-methylpiperazin-1-yl]methanone'>8FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><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'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5xvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xvg OCA], [http://pdbe.org/5xvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xvg RCSB], [http://www.ebi.ac.uk/pdbsum/5xvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xvg ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xvg OCA], [http://pdbe.org/5xvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xvg RCSB], [http://www.ebi.ac.uk/pdbsum/5xvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xvg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5xvg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5xvg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Li, H]]		[[Category: Li, H]]

OCA at 06:16, 7 February 2018

OCA — Wed, 07 Feb 2018 06:16:03 GMT

←Older revision		Revision as of 06:16, 7 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5xvg is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of PAK4 in complex with inhibitor CZH226==
		+	<StructureSection load='5xvg' size='340' side='right' caption='[[5xvg]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5xvg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XVG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8FX:[6-chloranyl-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]-[(3R)-3-methylpiperazin-1-yl]methanone'>8FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><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'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xvg OCA], [http://pdbe.org/5xvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xvg RCSB], [http://www.ebi.ac.uk/pdbsum/5xvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xvg ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PAK4_HUMAN PAK4_HUMAN]] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.<ref>PMID:11278822</ref> <ref>PMID:11313478</ref> <ref>PMID:14560027</ref> <ref>PMID:15660133</ref> <ref>PMID:20507994</ref> <ref>PMID:20805321</ref> <ref>PMID:20631255</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold. Based on the shape and chemical composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline series of inhibitors as a starting point. Guided by X-ray crystallography and a structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline-2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors' selectivity, therapeutic potency, and pharmaceutical properties were optimized. One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346-fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound potently inhibited the migration and invasion of A549 tumor cells by regulating the PAK4-directed downstream signaling pathways in vitro. Taken together, these data support the further development of 31 as a lead compound for PAK4-targeted anticancer drug discovery and as a valuable research probe for the further biological investigation of group II PAKs.

-	~~Authors: Zhao~~, F., Li, H.	+	Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors.,Hao C, Zhao F, Song H, Guo J, Li X, Jiang X, Huan R, Song S, Zhang Q, Wang R, Wang K, Pang Y, Liu T, Lu T, Huang W, Wang J, Lin B, He Z, Li H, Li F, Zhao D, Cheng M J Med Chem. 2018 Jan 11;61(1):265-285. doi: 10.1021/acs.jmedchem.7b01342. Epub, 2017 Dec 30. PMID:29190083<ref>PMID:29190083</ref>

-	~~Description: Crystal Structure~~ of ~~PAK4 in complex with inhibitor CZH226~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5xvg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Zhao, F]]		[[Category: Zhao, F]]
		+	[[Category: Atp binding pocket]]
		+	[[Category: Transferase]]

OCA: Protected "5xvg" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 15:49:34 GMT

Protected "5xvg" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:49, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5xvg is ON HOLD until Paper Publication Authors: Zhao, F., Li, H. Description: Crystal Structure of PAK4 in complex with inhibitor CZH226 [[Categor...

OCA — Wed, 27 Sep 2017 15:49:33 GMT

New page: '''Unreleased structure''' The entry 5xvg is ON HOLD until Paper Publication Authors: Zhao, F., Li, H. Description: Crystal Structure of PAK4 in complex with inhibitor CZH226 [[Categor...

New page

'''Unreleased structure'''

The entry 5xvg is ON HOLD until Paper Publication

Authors: Zhao, F., Li, H.

Description: Crystal Structure of PAK4 in complex with inhibitor CZH226
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Zhao, F]]