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Structural modification of NADPH oxidase activator (Noxa 1) by oxidative stress: An experimental and computational study.
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.ijbiomac.2020.09.120
Pankaj Attri 1 , Jae-Hyun Park 2 , Joey De Backer 3 , Myeongkyu Kim 2 , Ji-Hye Yun 2 , Yunseok Heo 2 , Sylvia Dewilde 3 , Masaharu Shiratani 4 , Eun Ha Choi 5 , Weontae Lee 2 , Annemie Bogaerts 6
Affiliation  

NADPH oxidases 1 (NOX1) derived reactive oxygen species (ROS) play an important role in the progression of cancer through signaling pathways. Therefore, in this paper, we demonstrate the effect of cold atmospheric plasma (CAP) on the structural changes of Noxa1 SH3 protein, one of the regulatory subunits of NOX1. For this purpose, firstly we purified the Noxa1 SH3 protein and analyzed the structure using X-ray crystallography, and subsequently, we treated the protein with two types of CAP reactors such as pulsed dielectric barrier discharge (DBD) and Soft Jet for different time intervals. The structural deformation of Noxa1 SH3 protein was analyzed by various experimental methods (circular dichroism, fluorescence, and NMR spectroscopy) and by MD simulations. Additionally, we demonstrate the effect of CAP (DBD and Soft Jet) on the viability and expression of NOX1 in A375 cancer cells. Our results are useful to understand the structural modification/oxidation occur in protein due to reactive oxygen and nitrogen (RONS) species generated by CAP.



中文翻译:

NADPH氧化酶激活剂(Noxa 1)通过氧化应激的结构修饰:一项实验和计算研究。

NADPH氧化酶1(NOX1)衍生的活性氧(ROS)通过信号传导途径在癌症进展中起重要作用。因此,在本文中,我们证明了冷大气血浆(CAP)对Noxa1 SH3蛋白(NOX1的调节亚基之一)的结构变化的影响。为此,我们首先纯化了Noxa1 SH3蛋白,并使用X射线晶体学对其结构进行了分析,然后,我们用两种类型的CAP反应器处理了该蛋白,例如脉冲介电势垒放电(DBD)和Soft Jet在不同的时间间隔。通过各种实验方法(圆二色性,荧光和NMR光谱)和MD模拟分析了Noxa1 SH3蛋白的结构变形。另外,我们证明了CAP(DBD和Soft Jet)对A375癌细胞的生存能力和NOX1表达的影响。我们的结果有助于理解由于CAP产生的活性氧和氮(RONS)物种而导致蛋白质发生的结构修饰/氧化。

更新日期:2020-09-20
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