Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil.
Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil.
复制标题
尿嘧啶的含硫和含硒类似物的氧化还原化学的比较。
DOI：
10.1016/j.freeradbiomed.2017.01.028
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发表时间：
2017-03
影响因子：
7.4
通讯作者：
Hondal RJ
中科院分区：
文献类型：
--
作者：
Payne NC;Geissler A;Button A;Sasuclark AR;Schroll AL;Ruggles EL;Gladyshev VN;Hondal RJ
硒以硒代半胱氨酸的形式存在于蛋白质中，其中该氨基酸起催化氧化还原酶的作用。硒代半胱氨酸在自然界中的应用与氧化还原催化密切相关。然而，在tRNAGlu、tRNAGln和tRNALys的摆动位置处的2-硒尿苷部分中也发现硒。据认为，由于硫和硒取代氧引起的物理化学变化，tRNA摆动位置的修饰提高了密码子-反密码子对的选择性。硒代半胱氨酸和2-硒代尿苷都有广泛的类似物，半胱氨酸和硫代尿苷，其中使用硫代替。为了研究硒在2-硒尿苷中的作用，我们采用1H-NMR、77 Se-NMR和液相色谱-质谱法对含硫的2-硫尿嘧啶-5-羧酸（s2 c5 Ura）及其硒类似物2-硒尿嘧啶-5-羧酸（se 2c 5 Ura）的氧化反应进行了比较分析。用过氧化氢处理s2 c5 Ura导致氧化的中间体，随后不可逆地脱硫以形成尿嘧啶-5-羧酸（c5 Ura）。与此相反，se 2c 5 Ura氧化导致二硒中间体，随后转化为亚硒酸，这两者都可以很容易地被抗坏血酸和谷胱甘肽还原。谷氨酸和抗坏血酸只最低限度地防止脱硫的s2 c5 Ura，而很少deselenization的se 2c 5 Ura发生在相同的抗氧化剂的存在下。此外，se 2c 5 Ura而不是s2 c5 Ura显示谷胱甘肽过氧化物酶活性，进一步表明se 2c 5 Ura的氧化是容易可逆的，而s2 c5 Ura的氧化不是。这些模型核碱基的研究结果表明，2-硒尿苷的使用与抗氧化失活有关，否则2-硫尿苷的特点。由于硒代半胱氨酸在蛋白质中的使用也赋予抗氧化性，我们的研究结果表明硒在生物学中的使用有一个共同的机制。
Selenium is present in proteins in the form of selenocysteine, where this amino acid serves catalytic oxidoreductase functions. The use of selenocysteine in nature is strongly associated with redox catalysis. However, selenium is also found in a 2-selenouridine moiety at the wobble position of tRNAGlu, tRNAGln and tRNALys. It is thought that the modifications of the wobble position of the tRNA improves the selectivity of the codon-anticodon pair as a result of the physico-chemical changes that result from substitution of sulfur and selenium for oxygen. Both selenocysteine and 2-selenouridine have widespread analogs, cysteine and thiouridine, where sulfur is used instead. To examine the role of selenium in 2-selenouridine, we comparatively analyzed the oxidation reactions of sulfur-containing 2-thiouracil-5-carboxylic acid (s2c5Ura) and its selenium analog 2-selenouracil-5-carboxylic acid (se2c5Ura) using 1H-NMR spectroscopy, 77Se-NMR spectroscopy, and liquid chromatography-mass spectrometry. Treatment of s2c5Ura with hydrogen peroxide led to oxidized intermediates, followed by irreversible desulfurization to form uracil-5-carboxylic acid (c5Ura). In contrast, se2c5Ura oxidation resulted in a diselenide intermediate, followed by conversion to the seleninic acid, both of which could be readily reduced by ascorbate and glutathione. Glutathione and ascorbate only minimally prevented desulfurization of s2c5Ura, whereas very little deselenization of se2c5Ura occurred in the presence of the same antioxidants. In addition, se2c5Ura but not s2c5Ura showed glutathione peroxidase activity, further suggesting that oxidation of se2c5Ura is readily reversible, while oxidation of s2c5Ura is not. The results of the study of these model nucleobases suggest that the use of 2-selenouridine is related to resistance to oxidative inactivation that otherwise characterizes 2-thiouridine. As the use of selenocysteine in proteins also confers resistance to oxidation, our findings suggest a common mechanism for the use of selenium in biology.