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首页> 外文期刊>Biochemistry >Molecular Level Interactions of S 100A 13 with Amlexanox: Inhibitor for Formation of the Multiprotein Complex in the Nonclassical Pathway of Acidic Fibroblast Growth Factor
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Molecular Level Interactions of S 100A 13 with Amlexanox: Inhibitor for Formation of the Multiprotein Complex in the Nonclassical Pathway of Acidic Fibroblast Growth Factor

机译:S 100A 13与氨纶的分子水平相互作用:酸性成纤维细胞生长因子非经典途径中多蛋白复合物形成的抑制剂。

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摘要

SIO0A13 and acidic fibroblast growth factor (FGFI) arc involved in a wide array of important biological processes, such as angiogenesis, cell differentiation, neurogenesis, and tumor growth. Generally, the biological function of FGFI is to recognize a specific tyrosine kinase on the cell surface and initiate the cell signal transduction cascade. Amlexanox (2-amino-7-isopropy1-5-oxo-5H-[1] benzopyrano[2,3-b]pyridine- 3-carboxylic acid) is an antiallergic drug that binds SI 00A13 and FGFI and inhibits the heat shock induced release of SIOOA13 and FGFI. In the present study, we investigated the interaction of amlexanox with S 1 00A13 using various biophysical techniques, including isothermal titration calorimetry, fluorescence spectrophotometry, and multidimensional NMR spectroscopy. We report the three-dimensional solution structure of the SIO0A13-amlexanox complex. These data show that amlexanox binds specifically to the FGF I -S100A13 interface and prevents the formation of the FGFI-releasing complex. In addition, we demonstrate that amlexanox acts as an antagonist of S 1 00A13 by binding to its FGFI binding site and subsequently inhibiting the nonclassical pathway of these proteins. This inhibition likely results in the ability of amlexanox to antagonize the angiogenic and mitogcnic activity of FGFI.
机译:SIO0A13和酸性成纤维细胞生长因子(FGFI)参与了许多重要的生物学过程,例如血管生成,细胞分化,神经发生和肿瘤生长。通常,FGFI的生物学功能是识别细胞表面上的特定酪氨酸激酶并启动细胞信号转导级联反应。 Amlexanox(2-氨基-7-异丙基1-5-氧代-5H- [1]苯并吡喃基[2,3-b]吡啶-3-羧酸)是一种抗过敏药,可结合SI 00A13和FGFI并抑制诱导的热激SIOOA13和FGFI的释放。在本研究中,我们使用各种生物物理技术(包括等温滴定热法,荧光分光光度法和多维NMR光谱法)研究了氨lexanox与S 1 00A13的相互作用。我们报告了SIO0A13-amlexanox复合体的三维解决方案结构。这些数据表明氨lexanox特异性结合至FGF I-S100A13界面,并阻止了FGFI释放复合物的形成。此外,我们证明氨lexanox通过与其FGFI结合位点结合并随后抑制这些蛋白质的非经典途径而充当S 1 00A13的拮抗剂。这种抑制作用可能导致氨lexanox拮抗FGFI的血管生成和线粒体活性的能力。

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