Structural and functional analyses of a sterol carrier protein in Spodoptera litura.
Structural and functional analyses of a sterol carrier protein in Spodoptera litura.
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DOI：
10.1371/journal.pone.0081542
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Feng Q
中科院分区：
文献类型：
--
作者：
Zhang L;Li D;Xu R;Zheng S;He H;Wan J;Feng Q
在昆虫中，胆固醇是细胞膜的组成成分之一，也是蜕皮激素生物合成的前体。由于昆虫在胆固醇生物合成途径中缺乏两种关键酶，角鲨烯合酶和羊毛甾醇合酶，它们不能自主地从简单化合物从头合成胆固醇，因此必须从它们的饮食中获得甾醇。固醇载体蛋白（SCP）是一种负责胆固醇吸收和转运的胆固醇结合蛋白。本研究构建了斜纹夜蛾（Spodoptera litura）SlSCPx-2的三维结构模型。甾醇和脂肪酸配体与SlSCPx-2的对接和ANS荧光置换实验表明，SlSCPx-2能够与胆固醇、硬脂酸、亚油酸、豆甾醇、油酸、棕榈酸和花生四烯酸等具有较高的亲和力，表明SlSCPx可能在植物吸收和转运这些胆固醇和脂肪酸中起重要作用。SlSCPx-2的定点突变分析表明，氨基酸残基F53、W 66、F89、F110、I115、T128和Q131对于SlSCPx-2蛋白的配体结合活性是关键的。虚拟配体筛选导致鉴定了几种先导化合物，它们是SlSCPx-2的潜在抑制剂。对筛选出的5个化合物进行抑菌活性测定，结果表明：AH-487/41731687、AG-664/14117324、AG-205/36813059和AG-205/07775053对S.斜纹夜蛾幼虫根据结构模型筛选出的化合物AH-487/41731687、AG-664/14117324、AG-205/36813059和AG-205/07775053与SlSCPx-2蛋白有较好的结合能力，并对S.斜纹夜蛾幼虫
In insects, cholesterol is one of the membrane components in cells and a precursor of ecdysteroid biosynthesis. Because insects lack two key enzymes, squalene synthase and lanosterol synthase, in the cholesterol biosynthesis pathway, they cannot autonomously synthesize cholesterol de novo from simple compounds and therefore have to obtain sterols from their diet. Sterol carrier protein (SCP) is a cholesterol-binding protein responsible for cholesterol absorption and transport. In this study, a model of the three-dimensional structure of SlSCPx-2 in Spodoptera litura, a destructive polyphagous agricultural pest insect in tropical and subtropical areas, was constructed. Docking of sterol and fatty acid ligands to SlSCPx-2 and ANS fluorescent replacement assay showed that SlSCPx-2 was able to bind with relatively high affinities to cholesterol, stearic acid, linoleic acid, stigmasterol, oleic acid, palmitic acid and arachidonate, implying that SlSCPx may play an important role in absorption and transport of these cholesterol and fatty acids from host plants. Site-directed mutation assay of SlSCPx-2 suggests that amino acid residues F53, W66, F89, F110, I115, T128 and Q131 are critical for the ligand-binding activity of the SlSCPx-2 protein. Virtual ligand screening resulted in identification of several lead compounds which are potential inhibitors of SlSCPx-2. Bioassay for inhibitory effect of five selected compounds showed that AH-487/41731687, AG-664/14117324, AG-205/36813059 and AG-205/07775053 inhibited the growth of S. litura larvae. Compounds AH-487/41731687, AG-664/14117324, AG-205/36813059 and AG-205/07775053 selected based on structural modeling showed binding affinity to SlSCPx-2 protein and inhibitory effect on the growth of S. litura larvae.
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影响因子：
2.6
作者：
Krebs, KC;Lan, Q
通讯作者：
Lan, Q
影响因子：
16
作者：
Stanley, Will A.;Filipp, Fabian V.;Wilmanns, Matthias
通讯作者：
Wilmanns, Matthias
DOI：
10.1107/s0907444902011745
发表时间：
2002-09-01
影响因子：
2.2
作者：
Lascombe, MB;Ponchet, M;Prangé, T
通讯作者：
Prangé, T
影响因子：
4.8
作者：
Schroeder, F;Frolov, A;Kier, AB
通讯作者：
Kier, AB
影响因子：
5.4
作者：
Viitanen, Lenita;Nylund, Matts;Edqvist, Johan
通讯作者：
Edqvist, Johan