预测 A2A 腺苷受体上的胆固醇相互作用位点。
Predictions for cholesterol interaction sites on the A2A adenosine receptor.
机构信息
Department of Physics and Astronomy, University of Delaware, Newark, Delaware 19716, USA.
出版信息
J Am Chem Soc. 2012 Oct 10;134(40):16512-5. doi: 10.1021/ja307532d. Epub 2012 Sep 26.
Abstract
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 confirmed by a just-published high-resolution structure of A(2A) cocrystallized with an antagonist.
摘要
对 A(2A) 腺苷受体进行的总计 1.4 μs 的分子动力学模拟清楚地表明了特定部位在介导结合态腺苷与胆固醇的 A(2A)相互作用中起关键作用。最强有力的证据是存在三个结合部位。其中两个位于细胞外小叶，一个部位与 VII 和 I 螺旋相互作用，另一个部位与 II 和 III 螺旋相互作用。一个部位位于细胞内小叶，与 III 和 IV 螺旋相互作用。我们预测的三个结合部位之一已被刚刚发表的 A(2A)与拮抗剂共晶的高分辨率结构所证实。
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