5ukm - Revision history

OCA at 13:29, 4 October 2023

OCA — Wed, 04 Oct 2023 13:29:03 GMT

←Older revision		Revision as of 13:29, 4 October 2023
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	<StructureSection load='5ukm' size='340' side='right'caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>		<StructureSection load='5ukm' size='340' side='right'caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ukm]] 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=5UKM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5UKM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ukm]] 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=5UKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UKM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T0E:5-[(3S,4R)-3-{[(2H-1,3-BENZODIOXOL-5-YL)OXY]METHYL}PIPERIDIN-4-YL]-2-FLUORO-N-[(1H-PYRAZOL-5-YL)METHYL]BENZAMIDE'>T0E</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]] 3.03Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRK2, ADRBK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), 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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T0E:5-[(3S,4R)-3-{[(2H-1,3-BENZODIOXOL-5-YL)OXY]METHYL}PIPERIDIN-4-YL]-2-FLUORO-N-[(1H-PYRAZOL-5-YL)METHYL]BENZAMIDE'>T0E</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=5ukm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ukm OCA], [https://pdbe.org/5ukm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ukm RCSB], [https://www.ebi.ac.uk/pdbsum/5ukm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ukm 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=5ukm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ukm OCA], [~~http~~://pdbe.org/5ukm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ukm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ukm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ukm ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ARBK1_BOVIN ARBK1_BOVIN]] 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 (By similarity). [[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_BOVIN ARBK1_BOVIN] 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 (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:
	==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: ~~Bovin~~]]	+	[[Category: Bos taurus]]
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cruz-Rodriguez, O]]	+	[[Category: Cruz-Rodriguez O]]
-	[[Category: Tesmer~~, J J.G]]~~	+	[[Category: Tesmer JJG]]
-	~~[[Category: Inhibitor complex]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-signaling protein complex~~]]	+

OCA at 09:30, 4 December 2019

OCA — Wed, 04 Dec 2019 09:30:17 GMT

←Older revision		Revision as of 09:30, 4 December 2019
Line 1:		Line 1:

	==bovine GRK2 in complex with human Gbetagamma subunits and CCG258208 (14as)==		==bovine GRK2 in complex with human Gbetagamma subunits and CCG258208 (14as)==
-	<StructureSection load='5ukm' size='340' side='right' caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>	+	<StructureSection load='5ukm' size='340' side='right'caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5ukm]] 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=5UKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKM FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ukm]] 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=5UKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKM FirstGlance]. <br>
Line 22:		Line 22:

	==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:
	[[Category: Bovin]]		[[Category: Bovin]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cruz-Rodriguez, O]]		[[Category: Cruz-Rodriguez, O]]
	[[Category: Tesmer, J J.G]]		[[Category: Tesmer, J J.G]]

OCA at 19:40, 15 November 2017

OCA — Wed, 15 Nov 2017 19:40:20 GMT

←Older revision		Revision as of 19:40, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='5ukm' size='340' side='right' caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>		<StructureSection load='5ukm' size='340' side='right' caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ukm]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ukm]] 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=5UKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T0E:5-[(3S,4R)-3-{[(2H-1,3-BENZODIOXOL-5-YL)OXY]METHYL}PIPERIDIN-4-YL]-2-FLUORO-N-[(1H-PYRAZOL-5-YL)METHYL]BENZAMIDE'>T0E</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T0E:5-[(3S,4R)-3-{[(2H-1,3-BENZODIOXOL-5-YL)OXY]METHYL}PIPERIDIN-4-YL]-2-FLUORO-N-[(1H-PYRAZOL-5-YL)METHYL]BENZAMIDE'>T0E</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRK2, ADRBK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), 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=5ukm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ukm OCA], [http://pdbe.org/5ukm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ukm RCSB], [http://www.ebi.ac.uk/pdbsum/5ukm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ukm 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=5ukm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ukm OCA], [http://pdbe.org/5ukm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ukm RCSB], [http://www.ebi.ac.uk/pdbsum/5ukm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ukm ProSAT]</span></td></tr>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5ukm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ukm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Transducin\|Transducin]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bovin]]
		+	[[Category: Human]]
	[[Category: Cruz-Rodriguez, O]]		[[Category: Cruz-Rodriguez, O]]
	[[Category: Tesmer, J J.G]]		[[Category: Tesmer, J J.G]]

OCA at 11:36, 12 April 2017

OCA — Wed, 12 Apr 2017 11:36:57 GMT

←Older revision		Revision as of 11:36, 12 April 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ukm is ~~ON HOLD~~	+	==bovine GRK2 in complex with human Gbetagamma subunits and CCG258208 (14as)==
		+	<StructureSection load='5ukm' size='340' side='right' caption='[[5ukm]], [[Resolution\|resolution]] 3.03Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ukm]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UKM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMT:O-METHYLCYSTEINE'>CMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=T0E:5-[(3S,4R)-3-{[(2H-1,3-BENZODIOXOL-5-YL)OXY]METHYL}PIPERIDIN-4-YL]-2-FLUORO-N-[(1H-PYRAZOL-5-YL)METHYL]BENZAMIDE'>T0E</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=5ukm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ukm OCA], [http://pdbe.org/5ukm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ukm RCSB], [http://www.ebi.ac.uk/pdbsum/5ukm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ukm ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ARBK1_BOVIN ARBK1_BOVIN]] 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 (By similarity). [[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 ==
		+	In heart failure, the beta-adrenergic receptors (betaARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart, making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure-based drug design approach, we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC50 of 30 nM against GRK2 and greater than 230-fold selectivity over other GRKs and kinases. Furthermore, 14as showed a 100-fold improvement in cardiomyocyte contractility assays over paroxetine and a plasma concentration higher than its IC50 for over 7 h. Three of these inhibitors, including 14as, were additionally crystallized in complex with GRK2 to give insights into the structural determinants of potency and selectivity of these inhibitors.

-	~~Authors~~:	+	Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.,Waldschmidt HV, Homan KT, Cato MC, Cruz-Rodriguez O, Cannavo A, Wilson MW, Song J, Cheung JY, Koch WJ, Tesmer JJ, Larsen SD J Med Chem. 2017 Mar 29. doi: 10.1021/acs.jmedchem.7b00112. PMID:28323425<ref>PMID:28323425</ref>

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

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

OCA — Wed, 01 Feb 2017 16:44:18 GMT

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

←Older revision

Revision as of 16:44, 1 February 2017

OCA: New page: '''Unreleased structure''' The entry 5ukm is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 01 Feb 2017 16:44:17 GMT

New page: '''Unreleased structure''' The entry 5ukm is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5ukm is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]