Pérez Edwin G, Cassels Bruce K, Zapata-Torres Gerald
Department of Chemistry, Faculty of Sciences, University of Chile, Casilla, Santiago, Chile.
Bioorg Med Chem Lett. 2009 Jan 1;19(1):251-4. doi: 10.1016/j.bmcl.2008.10.094. Epub 2008 Oct 25.
This study reports the comparative molecular modeling, docking and dynamic simulations of human alpha9alpha10 nicotinic acetylcholine receptors complexed with acetylcholine, nicotine and alpha-conotoxin RgIA, using as templates the crystal structures of Aplysia californica and Lymnaea stagnalis acetylcholine binding proteins. The molecular dynamics simulations showed that Arg112 in the complementary alpha10(-) subunit, is a determinant for recognition in the site that binds small ligands. However, Glu195 in the principal alpha9(+), and Asp114 in the complementary alpha10(-) subunit, might confer the potency and selectivity to alpha-conotoxin RgIA when interacting with Arg7 and Arg9 of this ligand.
本研究报告了以加州海兔和静水椎实螺乙酰胆碱结合蛋白的晶体结构为模板，对与乙酰胆碱、尼古丁和α-芋螺毒素RgIA复合的人α9α10烟碱型乙酰胆碱受体进行的比较分子建模、对接和动力学模拟。分子动力学模拟表明，互补α10(-)亚基中的Arg112是识别结合小配体位点的决定因素。然而，主要α9(+)亚基中的Glu195和互补α10(-)亚基中的Asp114在与该配体的Arg7和Arg9相互作用时，可能赋予α-芋螺毒素RgIA效力和选择性。
