7px4
From Proteopedia
(Difference between revisions)
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==Crystal structure of the adenosine A2A receptor (A2A-PSB1-bRIL) in complex with preladenant conjugate PSB-2113== | ==Crystal structure of the adenosine A2A receptor (A2A-PSB1-bRIL) in complex with preladenant conjugate PSB-2113== | ||
| - | <StructureSection load='7px4' size='340' side='right'caption='[[7px4]]' scene=''> | + | <StructureSection load='7px4' size='340' side='right'caption='[[7px4]], [[Resolution|resolution]] 2.25Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PX4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7px4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PX4 FirstGlance]. <br> |
| - | </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=7px4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7px4 OCA], [https://pdbe.org/7px4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7px4 RCSB], [https://www.ebi.ac.uk/pdbsum/7px4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7px4 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8E2:Preladenant+conjugate+PSB-2113'>8E2</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=7px4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7px4 OCA], [https://pdbe.org/7px4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7px4 RCSB], [https://www.ebi.ac.uk/pdbsum/7px4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7px4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://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 G protein-coupled adenosine A2A receptor (A2AAR) is an important new (potential) drug target in immuno-oncology, and for neurodegenerative diseases. Preladenant and its derivatives belong to the most potent A2AAR antagonists displaying exceptional selectivity. While crystal structures of the human A2AAR have been solved, mostly using the A2A-StaR2 protein that bears 9 point mutations, co-crystallization with Preladenant derivatives has so far been elusive. We developed a new A2AAR construct harboring a single point mutation (S913.39K) which renders it extremely thermostable. This allowed the co-crystallization of two novel Preladenant derivatives, the polyethylene glycol-conjugated (PEGylated) PSB-2113, and the fluorophore-labeled PSB-2115. The obtained crystal structures (2.25 A and 2.6 A resolution) provide explanations for the high potency and selectivity of Preladenant derivatives. They represent the first crystal structures of a GPCR in complex with PEG- and fluorophore-conjugated ligands. The applied strategy is predicted to be applicable to further class A GPCRs. | ||
| + | |||
| + | Single Stabilizing Point Mutation Enables High-Resolution Co-Crystal Structures of the Adenosine A2A Receptor with Preladenant Conjugates.,Claff T, Klapschinski TA, Subhramanyam UKT, Vaassen VJ, Schlegel JG, Vielmuth C, Voss JH, Labahn J, Muller CE Angew Chem Int Ed Engl. 2022 Feb 17. doi: 10.1002/anie.202115545. PMID:35174942<ref>PMID:35174942</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7px4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Claff T]] | + | [[Category: Claff, T]] |
| - | [[Category: Klapschinski | + | [[Category: Klapschinski, T A]] |
| - | [[Category: Labahn J]] | + | [[Category: Labahn, J]] |
| - | [[Category: Muller | + | [[Category: Muller, C E]] |
| - | [[Category: Schlegel | + | [[Category: Schlegel, J G]] |
| - | [[Category: | + | [[Category: Subhramanyam, U K.Tiruttani]] |
| - | [[Category: Vaassen | + | [[Category: Vaassen, V J]] |
| - | [[Category: Vielmuth C]] | + | [[Category: Vielmuth, C]] |
| - | [[Category: Voss | + | [[Category: Voss, J H]] |
| + | [[Category: A2a]] | ||
| + | [[Category: Adenosine receptor]] | ||
| + | [[Category: G protein-coupled receptor]] | ||
| + | [[Category: Gpcr]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Preladenant]] | ||
Revision as of 10:35, 6 April 2022
Crystal structure of the adenosine A2A receptor (A2A-PSB1-bRIL) in complex with preladenant conjugate PSB-2113
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