4yve - Revision history

OCA at 08:08, 27 September 2023

2023-09-27T08:08:03Z

←Older revision		Revision as of 08:08, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4yve]] 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=4YVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YVE FirstGlance]. <br>		<table><tr><td colspan='2'>[[4yve]] 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=4YVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YVE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</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]] 3.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [https://pdbe.org/4yve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [https://www.ebi.ac.uk/pdbsum/4yve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve 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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [https://pdbe.org/4yve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [https://www.ebi.ac.uk/pdbsum/4yve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:27, 10 May 2023

2023-05-10T07:27:59Z

←Older revision		Revision as of 07:27, 10 May 2023
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	==ROCK 1 bound to methoxyphenyl thiazole inhibitor==		==ROCK 1 bound to methoxyphenyl thiazole inhibitor==
-	<StructureSection load='4yve' size='340' side='right' caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>	+	<StructureSection load='4yve' size='340' side='right'caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4yve]] 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=4YVE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4YVE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4yve]] 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=4YVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YVE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yvc\|4yvc]]</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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [https://pdbe.org/4yve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [https://www.ebi.ac.uk/pdbsum/4yve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ROCK1 ([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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [~~http~~://pdbe.org/4yve PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4yve PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ROCK1_HUMAN ROCK1_HUMAN]] Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation.<ref>PMID:8617235</ref> <ref>PMID:9722579</ref> <ref>PMID:10436159</ref> <ref>PMID:10652353</ref> <ref>PMID:11018042</ref> <ref>PMID:11283607</ref> <ref>PMID:17158456</ref> <ref>PMID:18694941</ref> <ref>PMID:18573880</ref> <ref>PMID:19036714</ref> <ref>PMID:19181962</ref> <ref>PMID:19131646</ref> <ref>PMID:19997641</ref> <ref>PMID:21072057</ref>	+	[https://www.uniprot.org/uniprot/ROCK1_HUMAN ROCK1_HUMAN] Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation.<ref>PMID:8617235</ref> <ref>PMID:9722579</ref> <ref>PMID:10436159</ref> <ref>PMID:10652353</ref> <ref>PMID:11018042</ref> <ref>PMID:11283607</ref> <ref>PMID:17158456</ref> <ref>PMID:18694941</ref> <ref>PMID:18573880</ref> <ref>PMID:19036714</ref> <ref>PMID:19181962</ref> <ref>PMID:19131646</ref> <ref>PMID:19997641</ref> <ref>PMID:21072057</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Jacobs~~, M D]]~~	+	[[Category: Jacobs MD]]
-	~~[[Category: Dimer]]~~	+
-	~~[[Category: Dimerization]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Myosin]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:44, 18 July 2018

2018-07-18T08:44:42Z

←Older revision		Revision as of 08:44, 18 July 2018
Line 3:		Line 3:
	<StructureSection load='4yve' size='340' side='right' caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>		<StructureSection load='4yve' size='340' side='right' caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4yve]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4yve]] 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=4YVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yvc\|4yvc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yvc\|4yvc]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ROCK1 ([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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [http://pdbe.org/4yve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [http://www.ebi.ac.uk/pdbsum/4yve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve 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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [http://pdbe.org/4yve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [http://www.ebi.ac.uk/pdbsum/4yve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Jacobs, M D]]		[[Category: Jacobs, M D]]

OCA at 12:10, 12 April 2017

2017-04-12T12:10:52Z

←Older revision		Revision as of 12:10, 12 April 2017
Line 1:		Line 1:
		+
	==ROCK 1 bound to methoxyphenyl thiazole inhibitor==		==ROCK 1 bound to methoxyphenyl thiazole inhibitor==
	<StructureSection load='4yve' size='340' side='right' caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>		<StructureSection load='4yve' size='340' side='right' caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yvc\|4yvc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yvc\|4yvc]]</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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [http://www.ebi.ac.uk/pdbsum/4yve 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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [http://pdbe.org/4yve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [http://www.ebi.ac.uk/pdbsum/4yve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yve 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 4yve" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Rho-associated protein kinase\|Rho-associated protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:50, 17 June 2015

2015-06-17T08:50:29Z

←Older revision		Revision as of 08:50, 17 June 2015
Line 12:		Line 12:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~ROCK or~~ Rho~~-associated kinase, a~~ serine/threonine ~~kinase~~, ~~is an effector of Rho-dependent signaling~~ and ~~is involved~~ in ~~actin-cytoskeleton assembly and cell motility~~ and contraction~~. The ROCK protein consists of several domains: an N-terminal region~~, ~~a kinase catalytic domain~~, ~~a coiled-coil domain containing a RhoA binding site~~, and ~~a pleckstrin homology domain~~. ~~The C~~-~~terminal region~~ of ~~ROCK binds to and inhibits the kinase catalytic domains~~, and ~~this inhibition is reversed by binding RhoA, a small GTPase. Here we present the~~ structure ~~of the N~~-~~terminal region and the kinase domain. In our structure~~, ~~two N-terminal regions interact~~ to ~~form a dimerization domain linking two kinase domains together. This spatial arrangement presents the kinase active sites~~ and ~~regulatory sequences on a common face affording the possibility of both kinases simultaneously interacting with a dimeric inhibitory domain or with a dimeric substrate~~. ~~The kinase domain adopts a catalytically competent conformation; however, no phosphorylation of active site residues is observed~~ in ~~the structure. We also determined the structures of ROCK bound to four different ATP-competitive small molecule inhibitors (Y-27632~~, ~~fasudil, hydroxyfasudil, and H-1152P). Each of these compounds binds with reduced affinity to cAMP-dependent~~ kinase ~~(PKA)~~, ~~a highly homologous kinase. Subtle differences exist between the ROCK-~~ and ~~PKA-bound conformations of the inhibitors that suggest that interactions with a single amino acid of the active site (Ala215 in ROCK~~ and ~~Thr183~~ in ~~PKA) determine the relative selectivity of these compounds. Hydroxyfasudil, a metabolite of fasudil, may be selective for ROCK over PKA through a reversed binding orientation~~.	+	The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.

-	~~The structure~~ of ~~dimeric~~ ROCK ~~I reveals the mechanism for ligand selectivity~~.,~~Jacobs M~~, ~~Hayakawa K~~, ~~Swenson L~~, ~~Bellon S~~, ~~Fleming~~ M, Taslimi P, ~~Doran J~~ J ~~Biol~~ Chem. ~~2006 Jan 6;281(1):260-8. Epub 2005 Oct 24~~. PMID:~~16249185~~<ref>PMID:~~16249185~~</ref>	+	Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.,Green J, Cao J, Bandarage UK, Gao H, Court J, Marhefka C, Jacobs M, Taslimi P, Newsome D, Nakayama T, Shah S, Rodems S J Med Chem. 2015 Jun 12. PMID:26039570<ref>PMID:26039570</ref>

	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>

OCA at 14:00, 10 June 2015

2015-06-10T14:00:41Z

←Older revision		Revision as of 14:00, 10 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==ROCK 1 bound to methoxyphenyl thiazole inhibitor==
		+	<StructureSection load='4yve' size='340' side='right' caption='[[4yve]], [[Resolution\|resolution]] 3.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4yve]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4KK:2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]ACETAMIDE'>4KK</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yvc\|4yvc]]</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=4yve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yve OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yve RCSB], [http://www.ebi.ac.uk/pdbsum/4yve PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ROCK1_HUMAN ROCK1_HUMAN]] Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation.<ref>PMID:8617235</ref> <ref>PMID:9722579</ref> <ref>PMID:10436159</ref> <ref>PMID:10652353</ref> <ref>PMID:11018042</ref> <ref>PMID:11283607</ref> <ref>PMID:17158456</ref> <ref>PMID:18694941</ref> <ref>PMID:18573880</ref> <ref>PMID:19036714</ref> <ref>PMID:19181962</ref> <ref>PMID:19131646</ref> <ref>PMID:19997641</ref> <ref>PMID:21072057</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	ROCK or Rho-associated kinase, a serine/threonine kinase, is an effector of Rho-dependent signaling and is involved in actin-cytoskeleton assembly and cell motility and contraction. The ROCK protein consists of several domains: an N-terminal region, a kinase catalytic domain, a coiled-coil domain containing a RhoA binding site, and a pleckstrin homology domain. The C-terminal region of ROCK binds to and inhibits the kinase catalytic domains, and this inhibition is reversed by binding RhoA, a small GTPase. Here we present the structure of the N-terminal region and the kinase domain. In our structure, two N-terminal regions interact to form a dimerization domain linking two kinase domains together. This spatial arrangement presents the kinase active sites and regulatory sequences on a common face affording the possibility of both kinases simultaneously interacting with a dimeric inhibitory domain or with a dimeric substrate. The kinase domain adopts a catalytically competent conformation; however, no phosphorylation of active site residues is observed in the structure. We also determined the structures of ROCK bound to four different ATP-competitive small molecule inhibitors (Y-27632, fasudil, hydroxyfasudil, and H-1152P). Each of these compounds binds with reduced affinity to cAMP-dependent kinase (PKA), a highly homologous kinase. Subtle differences exist between the ROCK- and PKA-bound conformations of the inhibitors that suggest that interactions with a single amino acid of the active site (Ala215 in ROCK and Thr183 in PKA) determine the relative selectivity of these compounds. Hydroxyfasudil, a metabolite of fasudil, may be selective for ROCK over PKA through a reversed binding orientation.

-	The ~~entry 4yve is ON HOLD until Paper Publication~~	+	The structure of dimeric ROCK I reveals the mechanism for ligand selectivity.,Jacobs M, Hayakawa K, Swenson L, Bellon S, Fleming M, Taslimi P, Doran J J Biol Chem. 2006 Jan 6;281(1):260-8. Epub 2005 Oct 24. PMID:16249185<ref>PMID:16249185</ref>

-	~~Authors: Jacobs~~, M.D.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description:~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: Jacobs, M.D]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Jacobs, M D]]
		+	[[Category: Dimer]]
		+	[[Category: Dimerization]]
		+	[[Category: Kinase]]
		+	[[Category: Myosin]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:14, 13 May 2015

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	Authors: Jacobs, M.D.		Authors: Jacobs, M.D.

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-	Description: ~~ROCK 1 bound to methoxyphenyl thiazole inhibitor~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Jacobs, M.D]]		[[Category: Jacobs, M.D]]

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

2015-03-26T12:54:31Z

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

←Older revision

Revision as of 12:54, 26 March 2015

OCA: New page: '''Unreleased structure''' The entry 4yve is ON HOLD Authors: Jacobs, M.D. Description: ROCK 1 bound to methoxyphenyl thiazole inhibitor Category: Unreleased Structures [[Category:...

2015-03-26T12:54:29Z

New page: '''Unreleased structure''' The entry 4yve is ON HOLD Authors: Jacobs, M.D. Description: ROCK 1 bound to methoxyphenyl thiazole inhibitor Category: Unreleased Structures [[Category:...

New page

'''Unreleased structure'''

The entry 4yve is ON HOLD

Authors: Jacobs, M.D.

Description: ROCK 1 bound to methoxyphenyl thiazole inhibitor
[[Category: Unreleased Structures]]
[[Category: Jacobs, M.D]]