7pyr
From Proteopedia
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==Crystal structure of the adenosine A2A receptor (A2A-PSB1-bRIL) in complex with preladenant conjugate PSB-2115== | ==Crystal structure of the adenosine A2A receptor (A2A-PSB1-bRIL) in complex with preladenant conjugate PSB-2115== | ||
| - | <StructureSection load='7pyr' size='340' side='right'caption='[[7pyr]]' scene=''> | + | <StructureSection load='7pyr' size='340' side='right'caption='[[7pyr]], [[Resolution|resolution]] 2.60Å' 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=7PYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PYR FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PYR 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=7pyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pyr OCA], [https://pdbe.org/7pyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pyr RCSB], [https://www.ebi.ac.uk/pdbsum/7pyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pyr ProSAT]</span></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]] 2.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8IM:2-[2-[2-[2-[2-[2-[4-[4-[2-[7-azanyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.0^{2,6}]dodeca-1(9),2,4,7,11-pentaen-10-yl]ethyl]piperazin-1-yl]phenoxy]ethanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]-~{N}-[5-[2,2-bis(fluoranyl)-4,6,10,12-tetramethyl-1,3-diaza-2$l^{4}-boratricyclo[7.3.0.0^{3,7}]dodeca-4,6,9,11-tetraen-8-yl]pentyl]ethanamide'>8IM</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=7pyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pyr OCA], [https://pdbe.org/7pyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pyr RCSB], [https://www.ebi.ac.uk/pdbsum/7pyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pyr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <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> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7pyr" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Adenosine A2A receptor 3D structures|Adenosine A2A receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of the adenosine A2A receptor (A2A-PSB1-bRIL) in complex with preladenant conjugate PSB-2115
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