2y02: Difference between revisions
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==TURKEY BETA1 ADRENERGIC RECEPTOR WITH STABILISING MUTATIONS AND BOUND AGONIST CARMOTEROL== | |||
<StructureSection load='2y02' size='340' side='right' caption='[[2y02]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2y02]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Meleagris_gallopavo Meleagris gallopavo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y02 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2CV:HEGA-10'>2CV</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=WHJ:CARMOTEROL'>WHJ</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dep|1dep]], [[2vt4|2vt4]], [[2y01|2y01]], [[2y04|2y04]], [[2y00|2y00]], [[2y03|2y03]]</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=2y02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y02 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y02 RCSB], [http://www.ebi.ac.uk/pdbsum/2y02 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-adrenergic receptors (betaARs) are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins upon binding catecholamine agonist ligands such as adrenaline and noradrenaline. Synthetic ligands have been developed that either activate or inhibit betaARs for the treatment of asthma, hypertension or cardiac dysfunction. These ligands are classified as either full agonists, partial agonists or antagonists, depending on whether the cellular response is similar to that of the native ligand, reduced or inhibited, respectively. However, the structural basis for these different ligand efficacies is unknown. Here we present four crystal structures of the thermostabilized turkey (Meleagris gallopavo) beta(1)-adrenergic receptor (beta(1)AR-m23) bound to the full agonists carmoterol and isoprenaline and the partial agonists salbutamol and dobutamine. In each case, agonist binding induces a 1 A contraction of the catecholamine-binding pocket relative to the antagonist bound receptor. Full agonists can form hydrogen bonds with two conserved serine residues in transmembrane helix 5 (Ser(5.42) and Ser(5.46)), but partial agonists only interact with Ser(5.42) (superscripts refer to Ballesteros-Weinstein numbering). The structures provide an understanding of the pharmacological differences between different ligand classes, illuminating how GPCRs function and providing a solid foundation for the structure-based design of novel ligands with predictable efficacies. | |||
The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor.,Warne T, Moukhametzianov R, Baker JG, Nehme R, Edwards PC, Leslie AG, Schertler GF, Tate CG Nature. 2011 Jan 13;469(7329):241-4. PMID:21228877<ref>PMID:21228877</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Adrenergic receptor|Adrenergic receptor]] | *[[Adrenergic receptor|Adrenergic receptor]] | ||
*[[Beta-2 Adrenergic Receptor|Beta-2 Adrenergic Receptor]] | *[[Beta-2 Adrenergic Receptor|Beta-2 Adrenergic Receptor]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Meleagris gallopavo]] | [[Category: Meleagris gallopavo]] | ||
[[Category: Baker, J G | [[Category: Baker, J G]] | ||
[[Category: Edwards, P C | [[Category: Edwards, P C]] | ||
[[Category: Leslie, A G.W | [[Category: Leslie, A G.W]] | ||
[[Category: Moukhametzianov, R | [[Category: Moukhametzianov, R]] | ||
[[Category: Nehme, R | [[Category: Nehme, R]] | ||
[[Category: Schertler, G F.X | [[Category: Schertler, G F.X]] | ||
[[Category: Tate, C G | [[Category: Tate, C G]] | ||
[[Category: Warne, A | [[Category: Warne, A]] | ||
[[Category: G protein coupled receptor]] | [[Category: G protein coupled receptor]] | ||
[[Category: Gpcr]] | [[Category: Gpcr]] | ||
Revision as of 17:16, 18 December 2014
TURKEY BETA1 ADRENERGIC RECEPTOR WITH STABILISING MUTATIONS AND BOUND AGONIST CARMOTEROLTURKEY BETA1 ADRENERGIC RECEPTOR WITH STABILISING MUTATIONS AND BOUND AGONIST CARMOTEROL
Structural highlights
Publication Abstract from PubMedbeta-adrenergic receptors (betaARs) are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins upon binding catecholamine agonist ligands such as adrenaline and noradrenaline. Synthetic ligands have been developed that either activate or inhibit betaARs for the treatment of asthma, hypertension or cardiac dysfunction. These ligands are classified as either full agonists, partial agonists or antagonists, depending on whether the cellular response is similar to that of the native ligand, reduced or inhibited, respectively. However, the structural basis for these different ligand efficacies is unknown. Here we present four crystal structures of the thermostabilized turkey (Meleagris gallopavo) beta(1)-adrenergic receptor (beta(1)AR-m23) bound to the full agonists carmoterol and isoprenaline and the partial agonists salbutamol and dobutamine. In each case, agonist binding induces a 1 A contraction of the catecholamine-binding pocket relative to the antagonist bound receptor. Full agonists can form hydrogen bonds with two conserved serine residues in transmembrane helix 5 (Ser(5.42) and Ser(5.46)), but partial agonists only interact with Ser(5.42) (superscripts refer to Ballesteros-Weinstein numbering). The structures provide an understanding of the pharmacological differences between different ligand classes, illuminating how GPCRs function and providing a solid foundation for the structure-based design of novel ligands with predictable efficacies. The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor.,Warne T, Moukhametzianov R, Baker JG, Nehme R, Edwards PC, Leslie AG, Schertler GF, Tate CG Nature. 2011 Jan 13;469(7329):241-4. PMID:21228877[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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