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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Biophysical insights into the interaction of hen egg white lysozyme with therapeutic dye clofazimine: modulation of activity and SDS induced aggregation of model protein
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Biophysical insights into the interaction of hen egg white lysozyme with therapeutic dye clofazimine: modulation of activity and SDS induced aggregation of model protein

机译:生物物理见解母鸡蛋白溶菌酶与治疗染料氯氟氮的相互作用:活性调节和SDS诱导模型蛋白的聚集

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The present study details the binding process of clofazimine to hen egg white lysozyme (HEWL) using spectroscopy, dynamic light scattering, transmission electron microscopy (TEM), and molecular docking techniques. Clofazimine binds to the protein with binding constant (K-b) in the order of 1.57x10(4) at 298K. Binding process is spontaneous and exothermic. Molecular docking results suggested the involvement of hydrogen bonding and hydrophobic interactions in the binding process. Bacterial cell lytic activity in the presence of clofazimine increased to more than 40% of the value obtained with HEWL only. Interaction of the drug with HEWL induced ordered secondary structure in the protein and molecular compaction. Clofazimine also effectively inhibited the sodium dodecyl sulfate (SDS) induced amyloid formation in HEWL and caused disaggregation of preformed fibrils, reinforcing the notion that there is involvement of hydrophobic interactions and hydrogen bonding in the binding process of clofazimine with HEWL and clofazimine destabilizes the mature fibrils. Further, TEM images confirmed that fibrillar species were absent in the samples where amyloid induction was performed in the presence of clofazimine. As clofazimine is a drug less explored for the inhibition of fibril formation of the proteins, this study reports the inhibition of SDS-induced amyloid formation of HEWL by clofazimine, which will help in the development of clofazimine-related molecules for the treatment of amyloidosis.
机译:本研究详细介绍了使用光谱,动态光散射,透射电子显微镜(TEM)和分子对接技术的氯氟氮亚辛亚胺的结合过程。氯氟氮亚胺在298K时的1.57×10(4)的结合常数(K-B)结合蛋白质。绑定过程是自发性和放热的。分子对接结果表明氢键合和疏水相互作用在结合过程中的累积。在氯氟沙西亚胺存在下的细菌细胞裂解活性增加到仅具有HEWL获得的值的超过40%。药物与HEWL诱导有序二次结构在蛋白质中的相互作用和分子压实。 Clofazimine还有效地抑制了Hew1中的十二烷基硫酸钠(SDS)诱导的淀粉样蛋白形成,并引起了预成型的原纤维的分解,增强了疏水相互作用和氢键在氯氟氮与Hewl和Clofazimine的结合过程中的观念破坏了成熟的原纤维。此外,TEM图像证实了在氯氟氮存在下进行淀粉样蛋白诱导的样品中不存在纤维状物种。随着氯氟氮抑制蛋白质的抑制抑制蛋白质的毒品,本研究报告了氯氟氮酰胺对SDS诱导的SDS诱导的淀粉样蛋白形成的抑制,这将有助于在植物亚胺相关分子的发育中用于治疗淀粉样蛋白病。

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