5wg3 - Revision history

OCA at 14:12, 4 October 2023

OCA — Wed, 04 Oct 2023 14:12:16 GMT

←Older revision		Revision as of 14:12, 4 October 2023
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	<StructureSection load='5wg3' size='340' side='right'caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='5wg3' size='340' side='right'caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Bovin Bovin~~] and [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AFM:2-fluoro-5-[(3S,4R)-3-{[(1H-indazol-5-yl)oxy]methyl}piperidin-4-yl]-N-[(1H-pyrazol-3-yl)methyl]benzamide'>AFM</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]] 2.896Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRK2, ADRBK1, BARK, BARK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AFM:2-fluoro-5-[(3S,4R)-3-{[(1H-indazol-5-yl)oxy]methyl}piperidin-4-yl]-N-[(1H-pyrazol-3-yl)methyl]benzamide'>AFM</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/[Beta-adrenergic-receptor]_kinase [Beta-adrenergic-receptor] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.15 2.7.11.15] </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=5wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wg3 OCA], [https://pdbe.org/5wg3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wg3 RCSB], [https://www.ebi.ac.uk/pdbsum/5wg3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wg3 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=5wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wg3 OCA], [~~http~~://pdbe.org/5wg3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wg3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wg3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wg3 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ARBK1_HUMAN ARBK1_HUMAN]] Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner.<ref>PMID:19306925</ref> [[http://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [[http://www.uniprot.org/uniprot/GBB1_BOVIN GBB1_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.	+	[https://www.uniprot.org/uniprot/ARBK1_HUMAN ARBK1_HUMAN] Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner.<ref>PMID:19306925</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Beta adrenergic receptor kinase 3D structures\|Beta adrenergic receptor kinase 3D structures]]		*[[Beta adrenergic receptor kinase 3D structures\|Beta adrenergic receptor kinase 3D structures]]
		+	*[[Transducin 3D structures\|Transducin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bovin~~]]	+	[[Category: Bos taurus]]
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bouley, R]]	+	[[Category: Bouley R]]
-	[[Category: Tesmer~~, J J.G]]~~	+	[[Category: Tesmer JJG]]
-	~~[[Category: Transferase-signaling protein complex~~]]	+

OCA at 09:41, 4 December 2019

OCA — Wed, 04 Dec 2019 09:41:20 GMT

←Older revision		Revision as of 09:41, 4 December 2019
Line 1:		Line 1:

	==Human GRK2 in complex with Gbetagamma subunits and CCG258748==		==Human GRK2 in complex with Gbetagamma subunits and CCG258748==
-	<StructureSection load='5wg3' size='340' side='right' caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='5wg3' size='340' side='right'caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5wg3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wg3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta adrenergic receptor kinase 3D structures\|Beta adrenergic receptor kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	[[Category: Bovin]]		[[Category: Bovin]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bouley, R]]		[[Category: Bouley, R]]
	[[Category: Tesmer, J J.G]]		[[Category: Tesmer, J J.G]]
	[[Category: Transferase-signaling protein complex]]		[[Category: Transferase-signaling protein complex]]

OCA at 08:17, 17 January 2018

OCA — Wed, 17 Jan 2018 08:17:33 GMT

←Older revision		Revision as of 08:17, 17 January 2018
Line 3:		Line 3:
	<StructureSection load='5wg3' size='340' side='right' caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='5wg3' size='340' side='right' caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AFM:2-fluoro-5-[(3S,4R)-3-{[(1H-indazol-5-yl)oxy]methyl}piperidin-4-yl]-N-[(1H-pyrazol-3-yl)methyl]benzamide'>AFM</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=AFM:2-fluoro-5-[(3S,4R)-3-{[(1H-indazol-5-yl)oxy]methyl}piperidin-4-yl]-N-[(1H-pyrazol-3-yl)methyl]benzamide'>AFM</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">GRK2, ADRBK1, BARK, BARK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Beta-adrenergic-receptor]_kinase [Beta-adrenergic-receptor] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.15 2.7.11.15] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Beta-adrenergic-receptor]_kinase [Beta-adrenergic-receptor] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.15 2.7.11.15] </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=5wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wg3 OCA], [http://pdbe.org/5wg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wg3 RCSB], [http://www.ebi.ac.uk/pdbsum/5wg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wg3 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=5wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wg3 OCA], [http://pdbe.org/5wg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wg3 RCSB], [http://www.ebi.ac.uk/pdbsum/5wg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wg3 ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bovin]]
		+	[[Category: Human]]
	[[Category: Bouley, R]]		[[Category: Bouley, R]]
	[[Category: Tesmer, J J.G]]		[[Category: Tesmer, J J.G]]
	[[Category: Transferase-signaling protein complex]]		[[Category: Transferase-signaling protein complex]]

OCA at 08:29, 27 December 2017

OCA — Wed, 27 Dec 2017 08:29:05 GMT

←Older revision		Revision as of 08:29, 27 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5wg3 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human GRK2 in complex with Gbetagamma subunits and CCG258748==
		+	<StructureSection load='5wg3' size='340' side='right' caption='[[5wg3]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5wg3]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WG3 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AFM:2-fluoro-5-[(3S,4R)-3-{[(1H-indazol-5-yl)oxy]methyl}piperidin-4-yl]-N-[(1H-pyrazol-3-yl)methyl]benzamide'>AFM</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/[Beta-adrenergic-receptor]_kinase [Beta-adrenergic-receptor] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.15 2.7.11.15] </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=5wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wg3 OCA], [http://pdbe.org/5wg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wg3 RCSB], [http://www.ebi.ac.uk/pdbsum/5wg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wg3 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ARBK1_HUMAN ARBK1_HUMAN]] Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner.<ref>PMID:19306925</ref> [[http://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [[http://www.uniprot.org/uniprot/GBB1_BOVIN GBB1_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	G protein-coupled receptor kinases (GRKs) phosphorylate activated receptors to promote arrestin binding, decoupling from heterotrimeric G proteins, and internalization. GRK2 and GRK5 are overexpressed in the failing heart and thus have become therapeutic targets. Previously, we discovered two classes of GRK2-selective inhibitors, one stemming from GSK180736A, a Rho-associated coiled-coil containing kinase 1 (ROCK1) inhibitor, the other from paroxetine, a selective serotonin-reuptake inhibitor. These two classes of compounds bind to the GRK2 active site in a similar configuration but contain different hinge-binding "warheads": indazole and benzodioxole, respectively. We surmised from our prior studies that an indazole would be the stronger hinge binder and would impart increased potency when substituted for benzodioxole in paroxetine derivatives. To test this hypothesis, we synthesized a series of hybrid compounds that allowed us to compare the effects of inhibitors that differ only in the identity of the warhead. The indazole-paroxetine analogs were indeed more potent than their respective benzodioxole derivatives but lost selectivity. To investigate how these two warheads dictate selectivity, we determined the crystal structures of three of the indazole hybrid compounds (CCG224061, CCG257284, and CCG258748) in complex with GRK2-Gbetagamma Comparison of these structures with those of analogous benzodioxole-containing complexes confirmed that the indazole-paroxetine hybrids form stronger interactions with the hinge of the kinase but also stabilize a distinct conformation of the kinase domain of GRK2 compared with previous complexes with paroxetine analogs. This conformation is analogous to one that can be assumed by GRK5, at least partially explaining the loss in selectivity.

-	~~Authors~~:	+	Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors.,Bouley R, Waldschmidt HV, Cato MC, Cannavo A, Song J, Cheung JY, Yao XQ, Koch WJ, Larsen SD, Tesmer JJG Mol Pharmacol. 2017 Dec;92(6):707-717. doi: 10.1124/mol.117.110130. Epub 2017 Oct, 25. PMID:29070696<ref>PMID:29070696</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5wg3" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bouley, R]]
		+	[[Category: Tesmer, J J.G]]
		+	[[Category: Transferase-signaling protein complex]]

OCA: Protected "5wg3" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:47:45 GMT

Protected "5wg3" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:47, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wg3 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 14:47:44 GMT

New page: '''Unreleased structure''' The entry 5wg3 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5wg3 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]