5iu7: Difference between revisions
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The | ==Crystal structure of stabilized A2A adenosine receptor A2AR-StaR2-bRIL in complex with compound 12c at 1.9A resolution== | ||
<StructureSection load='5iu7' size='340' side='right' caption='[[5iu7]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5iu7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IU7 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6DY:2-(FURAN-2-YL)-N~5~-[2-(4-PHENYLPIPERIDIN-1-YL)ETHYL][1,2,4]TRIAZOLO[1,5-A][1,3,5]TRIAZINE-5,7-DIAMINE'>6DY</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iu4|5iu4]]</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=5iu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu7 OCA], [http://pdbe.org/5iu7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iu7 RCSB], [http://www.ebi.ac.uk/pdbsum/5iu7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN]] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The association and dissociation kinetics of ligands binding to proteins vary considerably, but the mechanisms behind this variability are poorly understood, limiting their utilization for drug discovery. This is particularly so for G protein-coupled receptors (GPCRs) where high resolution structural information is only beginning to emerge. Engineering the human A2A adenosine receptor has allowed structures to be solved in complex with the reference compound ZM241385 and four related ligands at high resolution. Differences between the structures are limited, with the most pronounced being the interaction of each ligand with a salt bridge on the extracellular side of the receptor. Mutagenesis experiments confirm the role of this salt bridge in controlling the dissociation kinetics of the ligands from the receptor, while molecular dynamics simulations demonstrate the ability of ligands to modulate salt bridge stability. These results shed light on a structural determinant of ligand dissociation kinetics and identify a means by which this property may be optimized. | |||
Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge Strength.,Segala E, Guo D, Cheng RK, Bortolato A, Deflorian F, Dore AS, Errey JC, Heitman LH, IJzerman AP, Marshall FH, Cooke RM J Med Chem. 2016 Jul 1. PMID:27312113<ref>PMID:27312113</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5iu7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bortolato, A]] | [[Category: Bortolato, A]] | ||
[[Category: Cooke, R | [[Category: Cheng, R K.Y]] | ||
[[Category: Cooke, R M]] | |||
[[Category: Deflorian, F]] | [[Category: Deflorian, F]] | ||
[[Category: Dore, A S]] | |||
[[Category: Errey, J C]] | |||
[[Category: Guo, D]] | [[Category: Guo, D]] | ||
[[Category: | [[Category: Heitman, L H]] | ||
[[Category: Ijzerman, A P]] | |||
[[Category: | [[Category: Marshall, F H]] | ||
[[Category: | |||
[[Category: Segala, E]] | [[Category: Segala, E]] | ||
[[Category: Chimera]] | |||
[[Category: G-protein-coupled receptor]] | |||
[[Category: Integral membrane protein]] | |||
[[Category: Membrane protein]] | |||
[[Category: Thermostabilizing mutation]] | |||
Revision as of 13:26, 13 July 2016
Crystal structure of stabilized A2A adenosine receptor A2AR-StaR2-bRIL in complex with compound 12c at 1.9A resolutionCrystal structure of stabilized A2A adenosine receptor A2AR-StaR2-bRIL in complex with compound 12c at 1.9A resolution
Structural highlights
Function[AA2AR_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedThe association and dissociation kinetics of ligands binding to proteins vary considerably, but the mechanisms behind this variability are poorly understood, limiting their utilization for drug discovery. This is particularly so for G protein-coupled receptors (GPCRs) where high resolution structural information is only beginning to emerge. Engineering the human A2A adenosine receptor has allowed structures to be solved in complex with the reference compound ZM241385 and four related ligands at high resolution. Differences between the structures are limited, with the most pronounced being the interaction of each ligand with a salt bridge on the extracellular side of the receptor. Mutagenesis experiments confirm the role of this salt bridge in controlling the dissociation kinetics of the ligands from the receptor, while molecular dynamics simulations demonstrate the ability of ligands to modulate salt bridge stability. These results shed light on a structural determinant of ligand dissociation kinetics and identify a means by which this property may be optimized. Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge Strength.,Segala E, Guo D, Cheng RK, Bortolato A, Deflorian F, Dore AS, Errey JC, Heitman LH, IJzerman AP, Marshall FH, Cooke RM J Med Chem. 2016 Jul 1. PMID:27312113[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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