4zy6 - Revision history

OCA at 07:46, 18 May 2023

OCA — Thu, 18 May 2023 07:46:19 GMT

←Older revision		Revision as of 07:46, 18 May 2023
Line 3:		Line 3:
	<StructureSection load='4zy6' size='340' side='right'caption='[[4zy6]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='4zy6' size='340' side='right'caption='[[4zy6]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zy6]] is a 2 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=4ZY6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZY6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zy6]] is a 2 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=4ZY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZY6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4T6:N~2~-[(7-CHLORO-1H-BENZIMIDAZOL-6-YL)METHYL]-N~4~-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)PYRIMIDINE-2,4-DIAMINE'>4T6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4T6:N~2~-[(7-CHLORO-1H-BENZIMIDAZOL-6-YL)METHYL]-N~4~-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)PYRIMIDINE-2,4-DIAMINE'>4T6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zy4\|4zy4]], [[4zy5\|4zy5]]</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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [https://pdbe.org/4zy6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [https://www.ebi.ac.uk/pdbsum/4zy6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zy6 ProSAT]</span></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='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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [~~http~~://pdbe.org/4zy6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zy6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zy6 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 25:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Rouge L]]
-	[[Category: Rouge, L]]	+	[[Category: Wang W]]
-	[[Category: Wang, W]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Pak1]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:27, 26 June 2019

OCA — Wed, 26 Jun 2019 08:27:08 GMT

←Older revision		Revision as of 08:27, 26 June 2019
Line 1:		Line 1:
		+
	==Crystal structure of P21-activated kinase 1 in complex with an inhibitor compound 29==		==Crystal structure of P21-activated kinase 1 in complex with an inhibitor compound 29==
-	<StructureSection load='4zy6' size='340' side='right' caption='[[4zy6]], [[Resolution\|resolution]] 2.15Å' scene=''>	+	<StructureSection load='4zy6' size='340' side='right'caption='[[4zy6]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zy6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZY6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zy6]] is a 2 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=4ZY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZY6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4T6:N~2~-[(7-CHLORO-1H-BENZIMIDAZOL-6-YL)METHYL]-N~4~-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)PYRIMIDINE-2,4-DIAMINE'>4T6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4T6:N~2~-[(7-CHLORO-1H-BENZIMIDAZOL-6-YL)METHYL]-N~4~-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)PYRIMIDINE-2,4-DIAMINE'>4T6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zy4\|4zy4]], [[4zy5\|4zy5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zy4\|4zy4]], [[4zy5\|4zy5]]</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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [http://pdbe.org/4zy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zy6 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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [http://pdbe.org/4zy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zy6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zy6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Rouge, L]]		[[Category: Rouge, L]]

OCA at 07:03, 16 December 2015

OCA — Wed, 16 Dec 2015 07:03:31 GMT

←Older revision		Revision as of 07:03, 16 December 2015
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zy4\|4zy4]], [[4zy5\|4zy5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zy4\|4zy4]], [[4zy5\|4zy5]]</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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zy6 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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [http://pdbe.org/4zy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zy6 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		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 4zy6" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 30:
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Pak1]]		[[Category: Pak1]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:33, 15 July 2015

OCA — Wed, 15 Jul 2015 07:33:38 GMT

←Older revision		Revision as of 07:33, 15 July 2015
Line 10:		Line 10:
	== 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 p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity. Early lead compounds contained a basic primary amine, which was found to be a major metabolic soft spot with in vivo clearance proceeding predominantly via N-acetylation. We succeeded in identifying replacements with improved metabolic stability, leading to compounds with lower in vivo rodent clearance and excellent group I PAK selectivity.
		+
		+	Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors.,Crawford JJ, Lee W, Aliagas I, Mathieu S, Hoeflich KP, Zhou W, Wang W, Rouge L, Murray L, La H, Liu N, Fan PW, Cheong J, Heise CE, Ramaswamy S, Mintzer R, Liu Y, Chao Q, Rudolph J J Med Chem. 2015 Jun 25;58(12):5121-36. doi: 10.1021/acs.jmedchem.5b00572. Epub, 2015 Jun 12. PMID:26030457<ref>PMID:26030457</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:27, 1 July 2015

OCA — Wed, 01 Jul 2015 12:27:13 GMT

←Older revision		Revision as of 12:27, 1 July 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Crystal structure of P21-activated kinase 1 in complex with an inhibitor compound 29==
-		+	<StructureSection load='4zy6' size='340' side='right' caption='[[4zy6]], [[Resolution\|resolution]] 2.15Å' scene=''>
-	~~The entry~~ 4zy6 is ~~ON HOLD~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4zy6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZY6 FirstGlance]. <br>
-	~~Authors~~: ~~Rouge~~, L., ~~Wang~~, W.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4T6:N~2~-[(7-CHLORO-1H-BENZIMIDAZOL-6-YL)METHYL]-N~4~-(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)PYRIMIDINE-2,4-DIAMINE'>4T6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zy4\|4zy4]], [[4zy5\|4zy5]]</td></tr>
-	~~Description~~: ~~Crystal structure~~ of ~~P21~~-~~activated~~ kinase 1 in complex ~~with an inhibitor compound 29~~	+	<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>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=4zy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zy6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zy6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zy6 PDBsum]</span></td></tr>
		+	</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: Rouge, L]]		[[Category: Rouge, L]]
	[[Category: Wang, W]]		[[Category: Wang, W]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Pak1]]

OCA: Protected "4zy6" [edit=sysop:move=sysop]

OCA — Wed, 27 May 2015 14:54:07 GMT

Protected "4zy6" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:54, 27 May 2015

OCA: New page: '''Unreleased structure''' The entry 4zy6 is ON HOLD Authors: Rouge, L., Wang, W. Description: Crystal structure of P21-activated kinase 1 in complex with an inhibitor compound 29 [[Ca...

OCA — Wed, 27 May 2015 14:54:05 GMT

New page: '''Unreleased structure''' The entry 4zy6 is ON HOLD Authors: Rouge, L., Wang, W. Description: Crystal structure of P21-activated kinase 1 in complex with an inhibitor compound 29 [[Ca...

New page

'''Unreleased structure'''

The entry 4zy6 is ON HOLD

Authors: Rouge, L., Wang, W.

Description: Crystal structure of P21-activated kinase 1 in complex with an inhibitor compound 29
[[Category: Unreleased Structures]]
[[Category: Rouge, L]]
[[Category: Wang, W]]