5i0b - Revision history

OCA at 08:19, 23 August 2023

OCA — Wed, 23 Aug 2023 08:19:05 GMT

←Older revision		Revision as of 08:19, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='5i0b' size='340' side='right'caption='[[5i0b]], [[Resolution\|resolution]] 3.09Å' scene=''>		<StructureSection load='5i0b' size='340' side='right'caption='[[5i0b]], [[Resolution\|resolution]] 3.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i0b]] 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=5I0B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I0B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i0b]] 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=5I0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I0B FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=67U:6-BROMO-2~~-[~~1-METHYL-3-(PROPAN-2-YL)-1H-PYRAZOL-4-YL~~]~~-1H-IMIDAZO[4,5-B~~]~~PYRIDINE'>67U</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]] 3.09Å</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=67U:6-BROMO-2-[1-METHYL-3-(PROPAN-2-YL)-1H-PYRAZOL-4-YL]-1H-IMIDAZO[4,5-B]PYRIDINE'>67U</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>~~[[~~Gene\|Gene:]]</b></td><td class="sblockDat">PAK4~~, ~~KIAA1142 ([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=5i0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i0b OCA], [https://pdbe.org/5i0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i0b RCSB], [https://www.ebi.ac.uk/pdbsum/5i0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i0b 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/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~~://proteopedia.org/fgij/fg.htm?mol=5i0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i0b OCA], [~~http~~://pdbe.org/5i0b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i0b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i0b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i0b 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 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Park SY]]
-	[[Category: Park~~, S Y]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inihibitor complex~~]]	+

OCA at 08:39, 27 May 2020

OCA — Wed, 27 May 2020 08:39:23 GMT

←Older revision		Revision as of 08:39, 27 May 2020
Line 1:		Line 1:

	==Structure of PAK4==		==Structure of PAK4==
-	<StructureSection load='5i0b' size='340' side='right' caption='[[5i0b]], [[Resolution\|resolution]] 3.09Å' scene=''>	+	<StructureSection load='5i0b' size='340' side='right'caption='[[5i0b]], [[Resolution\|resolution]] 3.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i0b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I0B OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I0B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i0b]] 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=5I0B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I0B FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67U:6-BROMO-2-[1-METHYL-3-(PROPAN-2-YL)-1H-PYRAZOL-4-YL]-1H-IMIDAZO[4,5-B]PYRIDINE'>67U</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=67U:6-BROMO-2-[1-METHYL-3-(PROPAN-2-YL)-1H-PYRAZOL-4-YL]-1H-IMIDAZO[4,5-B]PYRIDINE'>67U</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, KIAA1142 ([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=5i0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i0b OCA], [http://pdbe.org/5i0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i0b RCSB], [http://www.ebi.ac.uk/pdbsum/5i0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i0b 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=5i0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i0b OCA], [http://pdbe.org/5i0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i0b RCSB], [http://www.ebi.ac.uk/pdbsum/5i0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i0b ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5i0b" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i0b" 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: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Park, S Y]]		[[Category: Park, S Y]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inihibitor complex]]		[[Category: Transferase-transferase inihibitor complex]]

OCA at 19:00, 15 December 2016

OCA — Thu, 15 Dec 2016 19:00:25 GMT

←Older revision		Revision as of 19:00, 15 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i0b is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of PAK4==
		+	<StructureSection load='5i0b' size='340' side='right' caption='[[5i0b]], [[Resolution\|resolution]] 3.09Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i0b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I0B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I0B FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67U:6-BROMO-2-[1-METHYL-3-(PROPAN-2-YL)-1H-PYRAZOL-4-YL]-1H-IMIDAZO[4,5-B]PYRIDINE'>67U</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=5i0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i0b OCA], [http://pdbe.org/5i0b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i0b RCSB], [http://www.ebi.ac.uk/pdbsum/5i0b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i0b 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 ==
		+	p21-Activated kinases (PAKs) which belong to the family of ste20 serine/threonine protein kinases regulate cytoskeletal reorganization, cell motility, cell proliferation, and oncogenic transformation which are all related to the cellular functions during cancer induction and metastasis. The fact that PAK mutations are detected in multiple tumor tissues makes PAKs a novel therapeutic drug target. In this study, an imidazo[4,5-b]pyridine-based PAK4 inhibitor, KY-04045 (6-Bromo-2-(3-isopropyl-1-methyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridine), was discovered using a virtual site-directed fragment-based drug design and was validated using an inhibition assay. Although PAK4 affinity to KY-04045 seems much weaker than that of the reported PAK4 inhibitors, the location of KY-04045 is clearly defined in the structure of PAK4 co-crystallized with KY-04045. The crystal structure illustrates that the pyrazole and imidazopyridine rings of KY-04045 are sufficient for mediating PAK4 hinge loop interaction. Hence, we believe that KY-04045 can be exploited as a basic building block in designing novel imidazo[4,5-b]pyridine-based PAK4 inhibitors.

-	~~Authors: Park~~, ~~S.Y~~., Park, S.Y.	+	The discovery and the structural basis of an imidazo[4,5-b]pyridine-based p21-activated kinase 4 inhibitor.,Park JK, Kim S, Han YJ, Kim SH, Kang NS, Lee H, Park S Bioorg Med Chem Lett. 2016 Jun 1;26(11):2580-3. doi: 10.1016/j.bmcl.2016.04.037. , Epub 2016 Apr 16. PMID:27117431<ref>PMID:27117431</ref>

-	~~Description: Structure~~ of ~~PAK4~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Park, S.Y]]	+	<div class="pdbe-citations 5i0b" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Park, S Y]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inihibitor complex]]

OCA at 01:43, 10 March 2016

OCA — Thu, 10 Mar 2016 01:43:59 GMT

←Older revision		Revision as of 01:43, 10 March 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i0b is ON HOLD	+	The entry 5i0b is ON HOLD until Paper Publication

	Authors: Park, S.Y., Park, S.Y.		Authors: Park, S.Y., Park, S.Y.

OCA at 16:35, 26 February 2016

OCA — Fri, 26 Feb 2016 16:35:52 GMT

←Older revision		Revision as of 16:35, 26 February 2016
Line 3:		Line 3:
	The entry 5i0b is ON HOLD		The entry 5i0b is ON HOLD

-	Authors: Park, SY, Park, SY	+	Authors: Park, S.Y., Park, S.Y.

-	Description: PAK4	+	Description: Structure of PAK4
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Park, ~~Sy, Park, Sy~~]]	+	[[Category: Park, S.Y]]

OCA: Protected "5i0b" [edit=sysop:move=sysop]

OCA — Wed, 10 Feb 2016 16:00:57 GMT

Protected "5i0b" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:00, 10 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i0b is ON HOLD Authors: Park, SY, Park, SY Description: PAK4 Category: Unreleased Structures Category: Park, Sy, Park, Sy

OCA — Wed, 10 Feb 2016 16:00:56 GMT

New page: '''Unreleased structure''' The entry 5i0b is ON HOLD Authors: Park, SY, Park, SY Description: PAK4 Category: Unreleased Structures Category: Park, Sy, Park, Sy

New page

'''Unreleased structure'''

The entry 5i0b is ON HOLD

Authors: Park, SY, Park, SY

Description: PAK4
[[Category: Unreleased Structures]]
[[Category: Park, Sy, Park, Sy]]