5he1 - Revision history

OCA at 12:31, 6 March 2024

OCA — Wed, 06 Mar 2024 12:31:59 GMT

←Older revision		Revision as of 12:31, 6 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[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>		[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;">
-	== Publication Abstract from PubMed ==
-	G protein-coupled receptors (GPCRs) are central to many physiological processes. Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failure. GSK180736A, developed as a Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site. Guided by its binding pose overlaid with the binding pose of a known potent GRK2 inhibitor, Takeda103A, a library of hybrid inhibitors was developed. This campaign produced several compounds possessing high potency and selectivity for GRK2 over other GRK subfamilies, PKA, and ROCK1. The most selective compound, 12n (CCG-224406), had an IC50 for GRK2 of 130 nM, >700-fold selectivity over other GRK subfamilies, and no detectable inhibition of ROCK1. Four of the new inhibitors were crystallized with GRK2 to give molecular insights into the binding and kinase selectivity of this class of inhibitors.
-
-	Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors.,Waldschmidt HV, Homan KT, Cruz-Rodriguez O, Cato MC, Waninger-Saroni J, Larimore KM, Cannavo A, Song J, Cheung JY, Kirchhoff PD, Koch WJ, Tesmer JJ, Larsen SD J Med Chem. 2016 Apr 28;59(8):3793-807. doi: 10.1021/acs.jmedchem.5b02000. Epub, 2016 Apr 13. PMID:27050625<ref>PMID:27050625</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5he1" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 07:32, 9 August 2023

OCA — Wed, 09 Aug 2023 07:32:58 GMT

←Older revision		Revision as of 07:32, 9 August 2023
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	<StructureSection load='5he1' size='340' side='right'caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>		<StructureSection load='5he1' size='340' side='right'caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5he1]] is a 3 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=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5he1]] is a 3 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=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZS2:(4~{S})-4-[4-FLUORANYL-3-(ISOQUINOLIN-1-YLMETHYLCARBAMOYL)PHENYL]-~{N}-(1~{H}-INDAZOL-5-YL)-6-METHYL-2-OXIDANYLIDENE-3,4-DIHYDRO-1~{H}-PYRIMIDINE-5-CARBOXAMIDE'>ZS2</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]] 3.15Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5he0\|5he0]], [[5he2\|5he2]], [[5he3\|5he3]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZS2:(4~{S})-4-[4-FLUORANYL-3-(ISOQUINOLIN-1-YLMETHYLCARBAMOYL)PHENYL]-~{N}-(1~{H}-INDAZOL-5-YL)-6-METHYL-2-OXIDANYLIDENE-3,4-DIHYDRO-1~{H}-PYRIMIDINE-5-CARBOXAMIDE'>ZS2</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADRBK1, BARK, BARK1, GRK2 ([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=9606 HUMAN]), GNG2 ([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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [https://pdbe.org/5he1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [https://www.ebi.ac.uk/pdbsum/5he1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5he1 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/[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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [~~http~~://pdbe.org/5he1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5he1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5he1 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_HUMAN GBG2_HUMAN]] 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 (By similarity). [[http://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN]] 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.<ref>PMID:18611381</ref>	+	[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\|Transducin]]	+	*[[Transducin 3D structures\|Transducin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cato~~, M C~~]]	+	[[Category: Cato MC]]
-	[[Category: Tesmer~~, J J.G]]~~	+	[[Category: Tesmer JJG]]
-	~~[[Category: Inhibitor complex]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Ph]]~~	+
-	~~[[Category: Rg]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex]]~~	+
-	~~[[Category: Wd-40~~]]	+

OCA at 09:05, 4 December 2019

OCA — Wed, 04 Dec 2019 09:05:13 GMT

←Older revision		Revision as of 09:05, 4 December 2019
Line 1:		Line 1:

	==Human GRK2 in complex with Gbetagamma subunits and CCG224062==		==Human GRK2 in complex with Gbetagamma subunits and CCG224062==
-	<StructureSection load='5he1' size='340' side='right' caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>	+	<StructureSection load='5he1' size='340' side='right'caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5he1]] is a 3 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=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5he1]] is a 3 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=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>
Line 23:		Line 23:

	==See Also==		==See Also==
		+	*[[Beta adrenergic receptor kinase 3D structures\|Beta adrenergic receptor kinase 3D structures]]
	*[[Transducin\|Transducin]]		*[[Transducin\|Transducin]]
	== References ==		== References ==
Line 29:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cato, M C]]		[[Category: Cato, M C]]
	[[Category: Tesmer, J J.G]]		[[Category: Tesmer, J J.G]]

OCA at 09:58, 22 November 2017

OCA — Wed, 22 Nov 2017 09:58:35 GMT

←Older revision		Revision as of 09:58, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='5he1' size='340' side='right' caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>		<StructureSection load='5he1' size='340' side='right' caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5he1]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5he1]] is a 3 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=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZS2:(4~{S})-4-[4-FLUORANYL-3-(ISOQUINOLIN-1-YLMETHYLCARBAMOYL)PHENYL]-~{N}-(1~{H}-INDAZOL-5-YL)-6-METHYL-2-OXIDANYLIDENE-3,4-DIHYDRO-1~{H}-PYRIMIDINE-5-CARBOXAMIDE'>ZS2</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZS2:(4~{S})-4-[4-FLUORANYL-3-(ISOQUINOLIN-1-YLMETHYLCARBAMOYL)PHENYL]-~{N}-(1~{H}-INDAZOL-5-YL)-6-METHYL-2-OXIDANYLIDENE-3,4-DIHYDRO-1~{H}-PYRIMIDINE-5-CARBOXAMIDE'>ZS2</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5he0\|5he0]], [[5he2\|5he2]], [[5he3\|5he3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5he0\|5he0]], [[5he2\|5he2]], [[5he3\|5he3]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADRBK1, BARK, BARK1, GRK2 ([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=9606 HUMAN]), GNG2 ([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/[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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [http://pdbe.org/5he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [http://www.ebi.ac.uk/pdbsum/5he1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5he1 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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [http://pdbe.org/5he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [http://www.ebi.ac.uk/pdbsum/5he1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5he1 ProSAT]</span></td></tr>
Line 22:		Line 23:

	==See Also==		==See Also==
-	*[[Beta-adrenergic receptor kinase\|Beta-adrenergic receptor kinase]]
	*[[Transducin\|Transducin]]		*[[Transducin\|Transducin]]
	== References ==		== References ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Cato, M C]]		[[Category: Cato, M C]]
	[[Category: Tesmer, J J.G]]		[[Category: Tesmer, J J.G]]

OCA at 06:56, 6 October 2017

OCA — Fri, 06 Oct 2017 06:56:48 GMT

←Older revision		Revision as of 06:56, 6 October 2017
Line 7:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5he0\|5he0]], [[5he2\|5he2]], [[5he3\|5he3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5he0\|5he0]], [[5he2\|5he2]], [[5he3\|5he3]]</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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [http://pdbe.org/5he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [http://www.ebi.ac.uk/pdbsum/5he1 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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [http://pdbe.org/5he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [http://www.ebi.ac.uk/pdbsum/5he1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5he1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5he1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5he1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-adrenergic receptor kinase\|Beta-adrenergic receptor kinase]]
		+	*[[Transducin\|Transducin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:48, 15 May 2016

OCA — Sun, 15 May 2016 16:48:41 GMT

←Older revision		Revision as of 16:48, 15 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5he1 is ~~ON HOLD~~	+	==Human GRK2 in complex with Gbetagamma subunits and CCG224062==
		+	<StructureSection load='5he1' size='340' side='right' caption='[[5he1]], [[Resolution\|resolution]] 3.15Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5he1]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HE1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZS2:(4~{S})-4-[4-FLUORANYL-3-(ISOQUINOLIN-1-YLMETHYLCARBAMOYL)PHENYL]-~{N}-(1~{H}-INDAZOL-5-YL)-6-METHYL-2-OXIDANYLIDENE-3,4-DIHYDRO-1~{H}-PYRIMIDINE-5-CARBOXAMIDE'>ZS2</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5he0\|5he0]], [[5he2\|5he2]], [[5he3\|5he3]]</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=5he1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5he1 OCA], [http://pdbe.org/5he1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5he1 RCSB], [http://www.ebi.ac.uk/pdbsum/5he1 PDBsum]</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_HUMAN GBG2_HUMAN]] 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 (By similarity). [[http://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN]] 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.<ref>PMID:18611381</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	G protein-coupled receptors (GPCRs) are central to many physiological processes. Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failure. GSK180736A, developed as a Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site. Guided by its binding pose overlaid with the binding pose of a known potent GRK2 inhibitor, Takeda103A, a library of hybrid inhibitors was developed. This campaign produced several compounds possessing high potency and selectivity for GRK2 over other GRK subfamilies, PKA, and ROCK1. The most selective compound, 12n (CCG-224406), had an IC50 for GRK2 of 130 nM, >700-fold selectivity over other GRK subfamilies, and no detectable inhibition of ROCK1. Four of the new inhibitors were crystallized with GRK2 to give molecular insights into the binding and kinase selectivity of this class of inhibitors.

-	~~Authors: Cato~~, ~~M.C~~., Tesmer, J.J.G.	+	Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors.,Waldschmidt HV, Homan KT, Cruz-Rodriguez O, Cato MC, Waninger-Saroni J, Larimore KM, Cannavo A, Song J, Cheung JY, Kirchhoff PD, Koch WJ, Tesmer JJ, Larsen SD J Med Chem. 2016 Apr 28;59(8):3793-807. doi: 10.1021/acs.jmedchem.5b02000. Epub, 2016 Apr 13. PMID:27050625<ref>PMID:27050625</ref>

-	~~Description: Human GRK2 in complex with Gbetagamma subunits and CCG224062~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: Cato, M.C]]	+	<div class="pdbe-citations 5he1" style="background-color:#fffaf0;"></div>
-	[[Category: Tesmer, J.J.G]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cato, M C]]
		+	[[Category: Tesmer, J J.G]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Kinase]]
		+	[[Category: Ph]]
		+	[[Category: Rg]]
		+	[[Category: Transferase-transferase inhibitor complex]]
		+	[[Category: Wd-40]]

OCA: Protected "5he1" [edit=sysop:move=sysop]

OCA — Wed, 13 Jan 2016 18:54:42 GMT

Protected "5he1" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:54, 13 January 2016

OCA: New page: '''Unreleased structure''' The entry 5he1 is ON HOLD Authors: Cato, M.C., Tesmer, J.J.G. Description: Human GRK2 in complex with Gbetagamma subunits and CCG224062 [[Category: Unrelease...

OCA — Wed, 13 Jan 2016 18:54:41 GMT

New page: '''Unreleased structure''' The entry 5he1 is ON HOLD Authors: Cato, M.C., Tesmer, J.J.G. Description: Human GRK2 in complex with Gbetagamma subunits and CCG224062 [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 5he1 is ON HOLD

Authors: Cato, M.C., Tesmer, J.J.G.

Description: Human GRK2 in complex with Gbetagamma subunits and CCG224062
[[Category: Unreleased Structures]]
[[Category: Cato, M.C]]
[[Category: Tesmer, J.J.G]]