8cic
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of stabilized A2A adenosine receptor A2AR-StaR2-bRIL in complex with clinical candidate Etrumadenant== | |
| + | <StructureSection load='8cic' size='340' side='right'caption='[[8cic]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8cic]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CIC FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.102Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=U30:3-[2-azanyl-6-[1-[[6-(2-oxidanylpropan-2-yl)pyridin-2-yl]methyl]-1,2,3-triazol-4-yl]pyrimidin-4-yl]-2-methyl-benzenecarbonitrile'>U30</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=8cic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cic OCA], [https://pdbe.org/8cic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cic RCSB], [https://www.ebi.ac.uk/pdbsum/8cic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cic ProSAT]</span></td></tr> | ||
| + | </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.[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The G(s) protein-coupled adenosine A(2A) receptor (A(2A)AR) represents an emerging drug target for cancer immunotherapy. The clinical candidate Etrumadenant was developed as an A(2A)AR antagonist with ancillary blockade of the A(2B)AR subtype. It constitutes a unique chemotype featuring a poly-substituted 2-amino-4-phenyl-6-triazolylpyrimidine core structure. Herein, we report two crystal structures of the A(2A)AR in complex with Etrumadenant, obtained with differently thermostabilized A(2A)AR constructs. This led to the discovery of an unprecedented interaction, a hydrogen bond of T88(3.36) with the cyano group of Etrumadenant. T88(3.36) is mutated in most A(2A)AR constructs used for crystallization, which has prevented the discovery of its interactions. In-vitro characterization of Etrumadenant indicated low selectivity versus the A(1)AR subtype, which can be rationalized by the structural data. These results will facilitate the future design of AR antagonists with desired selectivity. Moreover, they highlight the advantages of the employed A(2A)AR crystallization construct that is devoid of ligand binding site mutations. | ||
| - | + | Crystal structure of adenosine A(2A) receptor in complex with clinical candidate Etrumadenant reveals unprecedented antagonist interaction.,Claff T, Schlegel JG, Voss JH, Vaassen VJ, Weisse RH, Cheng RKY, Markovic-Mueller S, Bucher D, Strater N, Muller CE Commun Chem. 2023 Jun 1;6(1):106. doi: 10.1038/s42004-023-00894-6. PMID:37264098<ref>PMID:37264098</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8cic" style="background-color:#fffaf0;"></div> |
| - | [[Category: Hennig | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cheng RKY]] | ||
| + | [[Category: Hennig M]] | ||
| + | [[Category: Markovic-Mueller S]] | ||
Current revision
Crystal structure of stabilized A2A adenosine receptor A2AR-StaR2-bRIL in complex with clinical candidate Etrumadenant
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