Format

Send to

Choose Destination
Structure. 2011 Sep 7;19(9):1283-93. doi: 10.1016/j.str.2011.06.014.

Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine.

Author information

1
Heptares Therapeutics Ltd, BioPark, Welwyn Garden City, Herts, AL7 3AX, UK.

Abstract

Methylxanthines, including caffeine and theophylline, are among the most widely consumed stimulant drugs in the world. These effects are mediated primarily via blockade of adenosine receptors. Xanthine analogs with improved properties have been developed as potential treatments for diseases such as Parkinson's disease. Here we report the structures of a thermostabilized adenosine A(2A) receptor in complex with the xanthines xanthine amine congener and caffeine, as well as the A(2A) selective inverse agonist ZM241385. The receptor is crystallized in the inactive state conformation as defined by the presence of a salt bridge known as the ionic lock. The complete third intracellular loop, responsible for G protein coupling, is visible consisting of extended helices 5 and 6. The structures provide new insight into the features that define the ligand binding pocket of the adenosine receptor for ligands of diverse chemotypes as well as the cytoplasmic regions that interact with signal transduction proteins.

PMID:
21885291
PMCID:
PMC3732996
DOI:
10.1016/j.str.2011.06.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center