Adenosine receptors are activated by the endogenous ligand adenosine (potentially inosine also at A3 receptors). Crystal structures for the antagonist-bound [1,2,3,4], agonist-bound [5,6,7] and G protein-bound A2A adenosine receptors [8] have been described. The structures of an antagonist-bound A1 receptor [9] and an adenosine-bound A1 receptor-Gi complex [10] have been resolved by cryo-electronmicroscopy. Another structure of an antagonist-bound A1 receptor obtained with X-ray crystallography has also been reported [11]. caffeine is a nonselective antagonist for adenosine receptors, while istradefylline, a selective A2A receptor antagonist, is on the market for the treatment of Parkinson's disease.
References
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Segala E, Guo D, Cheng RK, et al. Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge Strength. J Med Chem 2016;59:6470-9.
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Congreve M, Andrews SP, Doré AS, et al. Discovery of 1,2,4-triazine derivatives as adenosine A(2A) antagonists using structure based drug design. J Med Chem 2012;55:1898-903.
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Lebon G, Warne T, Edwards PC, et al. Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 2011;474:521-5.
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Glukhova A, Thal DM, Nguyen AT, et al. Structure of the Adenosine A1 Receptor Reveals the Basis for Subtype Selectivity. Cell 2017;168:867-877.e13.
Draper-Joyce CJ, Khoshouei M, Thal DM, et al. Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature 2018;558:559-563.
Cheng RKY, Segala E, Robertson N, et al. Structures of Human A1 and A2A Adenosine Receptors with Xanthines Reveal Determinants of Selectivity. Structure 2017;25:1275-1285.e4.
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