4njd - Revision history

OCA at 10:49, 31 August 2022

OCA — Wed, 31 Aug 2022 10:49:43 GMT

←Older revision		Revision as of 10:49, 31 August 2022
Line 1:		Line 1:

	==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==		==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==
-	<StructureSection load='4njd' size='340' side='right'caption='[[4njd]]~~, [[Resolution\|resolution]] 2.50Å~~' scene=''>	+	<StructureSection load='4njd' size='340' side='right'caption='[[4njd]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[4njd]] is a 1 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NJD FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NJD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</scene></td></tr>	+	</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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [https://pdbe.org/4njd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [https://www.ebi.ac.uk/pdbsum/4njd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd ProSAT]</span></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'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [https://pdbe.org/4njd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [https://www.ebi.ac.uk/pdbsum/4njd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[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;">
-	== Publication Abstract from PubMed ==
-	Functional versatility and elevated expression in cancers have endowed p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug target. In this study, a novel PAK4 inhibitor, KY-04031 (N2-(2-(1H-indol-3-yl)ethyl)-N4-(1H-indazol-5-yl)-6-methoxy-1,3,5-triazine-2,4-di amine), was discovered using a high-throughput screening. Analysis of the complex crystal structure illustrated that both indole and indazole of KY-04031 are responsible for PAK4 hinge interaction. Moreover, the molecule's triazine core was found to mimic the ribose of the natural ATP substrate. The cell-based anti-cancer potency of KY-04031 was less effective than the pyrroloaminopyrazoles; however, the unique molecular feature of KY-04031 can be exploited in designing new PAK4 inhibitors.
-
-	Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor.,Ryu BJ, Kim S, Min B, Kim KY, Lee JS, Park WJ, Lee H, Kim SH, Park S Cancer Lett. 2014 Apr 1. pii: S0304-3835(14)00193-1. doi:, 10.1016/j.canlet.2014.03.024. PMID:24704155<ref>PMID:24704155</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4njd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Park S]]
-	[[Category: Park, S]]	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 05:04, 25 August 2022

OCA — Thu, 25 Aug 2022 05:04:56 GMT

←Older revision		Revision as of 05:04, 25 August 2022
Line 3:		Line 3:
	<StructureSection load='4njd' size='340' side='right'caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4njd' size='340' side='right'caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4njd]] is a 1 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=4NJD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4NJD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4njd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NJD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PAK4 ([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'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [https://pdbe.org/4njd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [https://www.ebi.ac.uk/pdbsum/4njd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd 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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [~~http~~://pdbe.org/4njd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4njd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd 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 23:		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: Large Structures]]		[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 08:20, 10 April 2019

OCA — Wed, 10 Apr 2019 08:20:33 GMT

←Older revision		Revision as of 08:20, 10 April 2019
Line 1:		Line 1:

	==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==		==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==
-	<StructureSection load='4njd' size='340' side='right' caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='4njd' size='340' side='right'caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4njd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NJD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4njd]] is a 1 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=4NJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NJD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PAK4 ([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/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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://pdbe.org/4njd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd 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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://pdbe.org/4njd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Park, S]]		[[Category: Park, S]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 14:44, 4 August 2016

OCA — Thu, 04 Aug 2016 14:44:59 GMT

←Older revision		Revision as of 14:44, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==		==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==
	<StructureSection load='4njd' size='340' side='right' caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4njd' size='340' side='right' caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' 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=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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd 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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://pdbe.org/4njd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4njd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4njd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:13, 25 December 2014

OCA — Thu, 25 Dec 2014 10:13:55 GMT

←Older revision		Revision as of 10:13, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4njd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NJD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4njd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NJD FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</scene></td></tr>
-	<tr><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><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd 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=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd PDBsum]</span></td></tr>
-	<table>	+	</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 14:		Line 16:
	Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor.,Ryu BJ, Kim S, Min B, Kim KY, Lee JS, Park WJ, Lee H, Kim SH, Park S Cancer Lett. 2014 Apr 1. pii: S0304-3835(14)00193-1. doi:, 10.1016/j.canlet.2014.03.024. PMID:24704155<ref>PMID:24704155</ref>		Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor.,Ryu BJ, Kim S, Min B, Kim KY, Lee JS, Park WJ, Lee H, Kim SH, Park S Cancer Lett. 2014 Apr 1. pii: S0304-3835(14)00193-1. doi:, 10.1016/j.canlet.2014.03.024. PMID:24704155<ref>PMID:24704155</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Park, S.]]	+	[[Category: Park, S]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:07, 21 May 2014

OCA — Wed, 21 May 2014 09:07:57 GMT

←Older revision		Revision as of 09:07, 21 May 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of p21-activated kinase 4 with a novel inhibitor KY-04031==
		+	<StructureSection load='4njd' size='340' side='right' caption='[[4njd]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4njd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NJD FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NJD:N-(1H-INDAZOL-5-YL)-N-[2-(1H-INDOL-3-YL)ETHYL]-6-METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE'>NJD</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4njd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4njd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4njd RCSB], [http://www.ebi.ac.uk/pdbsum/4njd PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Functional versatility and elevated expression in cancers have endowed p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug target. In this study, a novel PAK4 inhibitor, KY-04031 (N2-(2-(1H-indol-3-yl)ethyl)-N4-(1H-indazol-5-yl)-6-methoxy-1,3,5-triazine-2,4-di amine), was discovered using a high-throughput screening. Analysis of the complex crystal structure illustrated that both indole and indazole of KY-04031 are responsible for PAK4 hinge interaction. Moreover, the molecule's triazine core was found to mimic the ribose of the natural ATP substrate. The cell-based anti-cancer potency of KY-04031 was less effective than the pyrroloaminopyrazoles; however, the unique molecular feature of KY-04031 can be exploited in designing new PAK4 inhibitors.

-	~~The entry 4njd is ON HOLD~~	+	Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor.,Ryu BJ, Kim S, Min B, Kim KY, Lee JS, Park WJ, Lee H, Kim SH, Park S Cancer Lett. 2014 Apr 1. pii: S0304-3835(14)00193-1. doi:, 10.1016/j.canlet.2014.03.024. PMID:24704155<ref>PMID:24704155</ref>

-	~~Authors~~: Park, S.	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Structure of p21~~-~~activated kinase 4 with a novel~~ inhibitor ~~KY-04031~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Park, S.]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

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

OCA — Wed, 20 Nov 2013 12:59:24 GMT

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

←Older revision

Revision as of 12:59, 20 November 2013

OCA: New page: '''Unreleased structure''' The entry 4njd is ON HOLD Authors: Park, S. Description: Structure of p21-activated kinase 4 with a novel inhibitor KY-04031

OCA — Wed, 20 Nov 2013 12:59:23 GMT

New page: '''Unreleased structure''' The entry 4njd is ON HOLD Authors: Park, S. Description: Structure of p21-activated kinase 4 with a novel inhibitor KY-04031

New page

'''Unreleased structure'''

The entry 4njd is ON HOLD

Authors: Park, S.

Description: Structure of p21-activated kinase 4 with a novel inhibitor KY-04031