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用分子对接模拟软件研究了肝素与孕激素受体的相互作用。以肝素中的一糖单位作为探针对孕激素受体蛋白进行搜索,获得肝素组成单位与孕激素受体的特异性结合模式。结果发现,2-O-硫酸-α-L 艾杜糖醛酸(2-O-sulfated iduronic acid,IdoA(2S))作为肝素的核心组成单糖之一,与孕激素受体的结合能力最好。分子对接结果显示 IdoA(2S)深入到孕激素受体的 helix2 和 helix 11 所包围的结合口袋,与孕激素受体结合结构域关键残基 Asn 719 形成稳固的氢键;并与孕激素受体结合结构域的关键残基 Met 909 残基侧链近距离接触,揭示了 IdoA(2S)可能具有的孕激素受体拮抗效应的分子作用机制。本模拟实验所建立的模型能够部分解释肝素抑制孕激素依赖性乳腺癌的现象,同时推测了其相应机理。
The interaction between heparin and progestin receptors was investigated using molecular docking software. Progesterone receptor protein was searched by using a sugar unit in heparin as a probe to obtain the specific binding mode of heparin composition unit and progesterone receptor. As a result, 2-O-sulfated iduronic acid (IdoA (2S)), one of the core components of heparin, has the highest binding ability to progesterone receptor it is good. The molecular docking results show that IdoA (2S) penetrates into the binding pocket surrounded by the helix2 and helix 11 of the progesterone receptor and forms a stable hydrogen bond with Asn 719, the key residue of the progesterone receptor binding domain, and binds progesterone receptor Close proximity of the side chain residues of Met 909, a key residue of the binding domain, revealed the molecular mechanism of action of IdoA (2S) which may have the progestin receptor antagonistic effect. The model established by this simulation experiment can partially explain the heparin inhibit progesterone-dependent breast cancer phenomenon, and at the same time speculate the corresponding mechanism.