A Review of the Catalytic Mechanism of Human Manganese Superoxide Dismutase.

A Review of the Catalytic Mechanism of Human Manganese Superoxide Dismutase.
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DOI:
10.3390/antiox7020025
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发表时间:
2018-01-30
期刊:
Antioxidants (Basel, Switzerland)
影响因子:
--
通讯作者:
Borgstahl GEO
Borgstahl GEO
中科院分区:
其他
文献类型:
--
作者:
Azadmanesh J;Borgstahl GEO

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超氧化物歧化酶(SOD)是保护细胞免受活性氧(ROS)侵害的必需抗氧化酶。SOD水平的降低或影响其催化活性的突变具有严重的表型后果。SOD通过与活性中心金属的循环氧化和还原反应将超氧化物转化为氧和过氧化氢来发挥其生物保护作用。SOD的突变可导致肺癌、结肠癌和淋巴系统癌,以及神经退行性疾病,如帕金森病和肌萎缩性侧索硬化症。虽然自1968年发现以来,SOD已被证明具有重要的生物学意义,但其催化功能的机理仍然难以捉摸。广泛的调查与众多的方法试图揭开SOD的催化工作,但实验的局限性阻碍了直接观察的机制。在这里,我们专注于人类MnSOD,在人体内保护免受ROS的最重要的酶。人MnSOD存在于线粒体基质中,高达90%的细胞ROS产生的位置。我们回顾目前的知识MnSOD酶的机制和正在进行的研究,以解决剩余的奥秘。
Superoxide dismutases (SODs) are necessary antioxidant enzymes that protect cells from reactive oxygen species (ROS). Decreased levels of SODs or mutations that affect their catalytic activity have serious phenotypic consequences. SODs perform their bio-protective role by converting superoxide into oxygen and hydrogen peroxide by cyclic oxidation and reduction reactions with the active site metal. Mutations of SODs can cause cancer of the lung, colon, and lymphatic system, as well as neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis. While SODs have proven to be of significant biological importance since their discovery in 1968, the mechanistic nature of their catalytic function remains elusive. Extensive investigations with a multitude of approaches have tried to unveil the catalytic workings of SODs, but experimental limitations have impeded direct observations of the mechanism. Here, we focus on human MnSOD, the most significant enzyme in protecting against ROS in the human body. Human MnSOD resides in the mitochondrial matrix, the location of up to 90% of cellular ROS generation. We review the current knowledge of the MnSOD enzymatic mechanism and ongoing studies into solving the remaining mysteries.
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