4zji - Revision history

OCA at 11:33, 9 May 2024

2024-05-09T11:33:21Z

←Older revision		Revision as of 11:33, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zji]] is a 4 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=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zji]] is a 4 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=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.99Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [https://pdbe.org/4zji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [https://www.ebi.ac.uk/pdbsum/4zji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji 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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [https://pdbe.org/4zji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [https://www.ebi.ac.uk/pdbsum/4zji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:30, 18 May 2023

2023-05-18T07:30:29Z

←Older revision		Revision as of 07:30, 18 May 2023
Line 3:		Line 3:
	<StructureSection load='4zji' size='340' side='right'caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>		<StructureSection load='4zji' size='340' side='right'caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zji]] is a 4 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=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zji]] is a 4 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=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PAK1 ([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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [https://pdbe.org/4zji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [https://www.ebi.ac.uk/pdbsum/4zji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji 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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [~~http~~://pdbe.org/4zji PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zji PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PAK1_HUMAN PAK1_HUMAN]] Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2.<ref>PMID:8805275</ref> <ref>PMID:9395435</ref> <ref>PMID:9032240</ref> <ref>PMID:9528787</ref> <ref>PMID:10551809</ref> <ref>PMID:11733498</ref> <ref>PMID:12624090</ref> <ref>PMID:12876277</ref> <ref>PMID:14585966</ref> <ref>PMID:15611088</ref> <ref>PMID:15831477</ref> <ref>PMID:16278681</ref> <ref>PMID:17726028</ref> <ref>PMID:17989089</ref> <ref>PMID:22669945</ref>	+	[https://www.uniprot.org/uniprot/PAK1_HUMAN PAK1_HUMAN] Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2.<ref>PMID:8805275</ref> <ref>PMID:9395435</ref> <ref>PMID:9032240</ref> <ref>PMID:9528787</ref> <ref>PMID:10551809</ref> <ref>PMID:11733498</ref> <ref>PMID:12624090</ref> <ref>PMID:12876277</ref> <ref>PMID:14585966</ref> <ref>PMID:15611088</ref> <ref>PMID:15831477</ref> <ref>PMID:16278681</ref> <ref>PMID:17726028</ref> <ref>PMID:17989089</ref> <ref>PMID:22669945</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Gutmann S]]
-	[[Category: Gutmann, S]]	+	[[Category: Rummel G]]
-	[[Category: Rummel, G]]	+
-	~~[[Category: Allosteric]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Pak1]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:27, 26 June 2019

2019-06-26T08:27:52Z

←Older revision		Revision as of 08:27, 26 June 2019
Line 1:		Line 1:

	==PAK1 in complex with 2-chloro-5-ethyl-8-fluoro-11-(4-methylpiperazin-1-yl)-dibenzodiazepine==		==PAK1 in complex with 2-chloro-5-ethyl-8-fluoro-11-(4-methylpiperazin-1-yl)-dibenzodiazepine==
-	<StructureSection load='4zji' size='340' side='right' caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>	+	<StructureSection load='4zji' size='340' side='right'caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zji]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zji]] is a 4 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=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PAK1 ([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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [http://pdbe.org/4zji PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [http://www.ebi.ac.uk/pdbsum/4zji PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji 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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [http://pdbe.org/4zji PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [http://www.ebi.ac.uk/pdbsum/4zji PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji ProSAT]</span></td></tr>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4zji" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4zji" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== 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: Gutmann, S]]		[[Category: Gutmann, S]]

OCA at 13:28, 4 May 2017

2017-05-04T13:28:32Z

←Older revision		Revision as of 13:28, 4 May 2017
Line 1:		Line 1:
		+
	==PAK1 in complex with 2-chloro-5-ethyl-8-fluoro-11-(4-methylpiperazin-1-yl)-dibenzodiazepine==		==PAK1 in complex with 2-chloro-5-ethyl-8-fluoro-11-(4-methylpiperazin-1-yl)-dibenzodiazepine==
	<StructureSection load='4zji' size='340' side='right' caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>		<StructureSection load='4zji' size='340' side='right' caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [http://www.ebi.ac.uk/pdbsum/4zji 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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [http://pdbe.org/4zji PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [http://www.ebi.ac.uk/pdbsum/4zji PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zji ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4zji" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:21, 29 July 2015

2015-07-29T08:21:52Z

←Older revision		Revision as of 08:21, 29 July 2015
Line 9:		Line 9:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PAK1_HUMAN PAK1_HUMAN]] Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2.<ref>PMID:8805275</ref> <ref>PMID:9395435</ref> <ref>PMID:9032240</ref> <ref>PMID:9528787</ref> <ref>PMID:10551809</ref> <ref>PMID:11733498</ref> <ref>PMID:12624090</ref> <ref>PMID:12876277</ref> <ref>PMID:14585966</ref> <ref>PMID:15611088</ref> <ref>PMID:15831477</ref> <ref>PMID:16278681</ref> <ref>PMID:17726028</ref> <ref>PMID:17989089</ref> <ref>PMID:22669945</ref>		[[http://www.uniprot.org/uniprot/PAK1_HUMAN PAK1_HUMAN]] Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2.<ref>PMID:8805275</ref> <ref>PMID:9395435</ref> <ref>PMID:9032240</ref> <ref>PMID:9528787</ref> <ref>PMID:10551809</ref> <ref>PMID:11733498</ref> <ref>PMID:12624090</ref> <ref>PMID:12876277</ref> <ref>PMID:14585966</ref> <ref>PMID:15611088</ref> <ref>PMID:15831477</ref> <ref>PMID:16278681</ref> <ref>PMID:17726028</ref> <ref>PMID:17989089</ref> <ref>PMID:22669945</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels of selectivity across the kinome. Herein we report our structure-based optimization strategy of a dibenzodiazepine hit 1, discovered in a fragment-based screen, yielding highly potent and selective inhibitors of PAK1 such as 2 and 3. Compound 2 was cocrystallized with PAK1 to confirm binding to an allosteric site and to reveal novel key interactions. Compound 3 modulated PAK1 at the cellular level and due to its selectivity enabled valuable research to interrogate biological functions of the PAK1 kinase.
		+
		+	Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor.,Karpov AS, Amiri P, Bellamacina C, Bellance MH, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I, Guerro-Lagasse S, Gutmann S, Hinh L, Jahnke W, Klopp J, Lai A, Lindvall MK, Ma S, Mobitz H, Pecchi S, Rummel G, Shoemaker K, Trappe J, Voliva C, Cowan-Jacob SW, Marzinzik AL ACS Med Chem Lett. 2015 May 22;6(7):776-81. doi: 10.1021/acsmedchemlett.5b00102. , eCollection 2015 Jul 9. PMID:26191365<ref>PMID:26191365</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:04, 24 June 2015

2015-06-24T13:04:40Z

←Older revision		Revision as of 13:04, 24 June 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==PAK1 in complex with 2-chloro-5-ethyl-8-fluoro-11-(4-methylpiperazin-1-yl)-dibenzodiazepine==
-		+	<StructureSection load='4zji' size='340' side='right' caption='[[4zji]], [[Resolution\|resolution]] 1.99Å' scene=''>
-	~~The entry~~ 4zji is ~~ON HOLD~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4zji]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJI FirstGlance]. <br>
-	~~Authors~~: ~~Gutmann~~, S., ~~Rummel~~, G.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4OQ:2-CHLORO-5-ETHYL-8-FLUORO-11-(4-METHYLPIPERAZIN-1-YL)-DIBENZODIAZEPINE'>4OQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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>
-	~~Description~~:	+	<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=4zji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zji OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zji RCSB], [http://www.ebi.ac.uk/pdbsum/4zji PDBsum]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PAK1_HUMAN PAK1_HUMAN]] Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2.<ref>PMID:8805275</ref> <ref>PMID:9395435</ref> <ref>PMID:9032240</ref> <ref>PMID:9528787</ref> <ref>PMID:10551809</ref> <ref>PMID:11733498</ref> <ref>PMID:12624090</ref> <ref>PMID:12876277</ref> <ref>PMID:14585966</ref> <ref>PMID:15611088</ref> <ref>PMID:15831477</ref> <ref>PMID:16278681</ref> <ref>PMID:17726028</ref> <ref>PMID:17989089</ref> <ref>PMID:22669945</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Gutmann, S]]		[[Category: Gutmann, S]]
	[[Category: Rummel, G]]		[[Category: Rummel, G]]
		+	[[Category: Allosteric]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Pak1]]
		+	[[Category: Transferase]]

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

2015-05-06T11:49:56Z

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

←Older revision

Revision as of 11:49, 6 May 2015

OCA: New page: '''Unreleased structure''' The entry 4zji is ON HOLD Authors: Gutmann, S., Rummel, G. Description: Category: Unreleased Structures Category: Gutmann, S Category: Rummel, G

2015-05-06T11:49:55Z

New page: '''Unreleased structure''' The entry 4zji is ON HOLD Authors: Gutmann, S., Rummel, G. Description: Category: Unreleased Structures Category: Gutmann, S Category: Rummel, G

New page

'''Unreleased structure'''

The entry 4zji is ON HOLD

Authors: Gutmann, S., Rummel, G.

Description:
[[Category: Unreleased Structures]]
[[Category: Gutmann, S]]
[[Category: Rummel, G]]