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Predictions for cholesterol interaction sites on the A2A adenosine receptor.

ABSTRACT: Molecular dynamics simulations of the A(2A) adenosine receptor totaling 1.4 ?s show clear evidence for specific sites mediating interactions between adenosine-bound A(2A) and cholesterol. The strongest evidence is for three binding sites. Two are in the extracellular leaflet, with one site interacting with helices VII and I, and the other with helices II and III. One site is located in the intracellular leaflet, interacting with helices III and IV. One of our three predicted binding sites is confirmed by a just-published high-resolution structure of A(2A) cocrystallized with an antagonist.

SUBMITTER: Lee JY

PROVIDER: S-EPMC3652312 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Predictions for cholesterol interaction sites on the A2A adenosine receptor.

Lee Ji Young JY Lyman Edward E

Journal of the American Chemical Society 20120926 40

Molecular dynamics simulations of the A(2A) adenosine receptor totaling 1.4 μs show clear evidence for specific sites mediating interactions between adenosine-bound A(2A) and cholesterol. The strongest evidence is for three binding sites. Two are in the extracellular leaflet, with one site interacting with helices VII and I, and the other with helices II and III. One site is located in the intracellular leaflet, interacting with helices III and IV. One of our three predicted binding sites is con ...[more]

PMID: 23005256

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