Selenium redox biochemistry of zinc-sulfur coordination sites in proteins and enzymes
Selenium redox biochemistry of zinc-sulfur coordination sites in proteins and enzymes
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DOI：
10.1073/pnas.96.5.1910
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Vallee, BL
中科院分区：
文献类型：
--
作者：
Jacob, C;Maret, W;Vallee, BL
硒已被越来越多地认为是生物和医学中的一种必需元素。它的生物化学与硫相似，但由于氧化还原电位和氧化态的稳定性而不同。硒可以替代半胱氨酸中普遍存在的硫，因此在十几种硒蛋白中扮演着重要的角色。我们选择检测锌硫中心作为硒氧化还原生物化学的可能靶点。硒化合物从锌/硫酸盐配位环境中释放锌，从而影响细胞中硫醇的氧化还原状态和锌的分布，并可能影响其他金属离子的分布。芳香硒化合物是其他相对不稳定的功能硒基团的很好的光谱探针。锌配位的硫代硫酸盐，例如金属硫蛋白(MT)，和非配位的硫代硫酸盐，例如谷胱甘肽，与苯基亚硒酸(氧化态+2)、苯基亚硒酰氯(氧化态0)和硒半胱胺(氧化态-1)反应。亚化学计量法和1：1化学计量法分别以亚化学计量比和1：1化学计量比分别与MT反应非常迅速，Se化合物还在过氧化反应和硫代/二硫化物交换反应中催化MT释放锌。在叔丁基氢过氧化氢的存在下，硒酶谷胱甘肽过氧化物酶催化氧化MT并释放锌，这表明这种类型的氧化还原化学可能用于生物学中控制金属代谢。此外，硒化合物很可能是体内锌/硫酸盐配位中心的靶标，因为过量的谷胱甘肽只部分抑制了这些反应。这种特异性和在低浓度下发生催化反应的可能性表明，锌的释放是硒化合物在抗炎和抗癌药物中治疗抗氧化作用的一个重要方面。
Selenium has been increasingly recognized as an essential element in biology and medicine. Its biochemistry resembles that of sulfur, yet differs from it by virtue of both redox potentials and stabilities of its oxidation states. Selenium can substitute for the more ubiquitous sulfur of cysteine and as such plays an important role in more than a dozen selenoproteins. We have chosen to examine zinc-sulfur centers as possible targets of selenium redox biochemistry. Selenium compounds release zinc from zinc/thiolate-coordination environments, thereby affecting the cellular thiol redox state and the distribution of zinc and likely of other metal ions. Aromatic selenium compounds are excellent spectroscopic probes of the otherwise relatively unstable functional selenium groups. Zinc-coordinated thiolates, e.g., metallothionein (MT), and uncoordinated thiolates, e.g., glutathione, react with benzeneseleninic acid (oxidation state +2), benzeneselenenyl chloride (oxidation state 0) and selenocystamine (oxidation state -1). Benzeneseleninic acid and benzeneselenenyl chloride react very rapidly with MT and titrate substoichiometrically and with a 1:1 stoichiometry, respectively, Selenium compounds also catalyze the release of zinc from MT in peroxidation and thio/disulfide-interchange reactions. The selenoenzyme glutathione peroxidase catalytically oxidizes MT and releases zinc in the presence of t-butyl hydroperoxide, suggesting that this type of redox chemistry may be employed in biology for the control of metal metabolism. Moreover, selenium compounds are likely targets for zinc/thiolate coordination centers in vivo, because the reactions are only partially suppressed by excess glutathione. This specificity and the potential to undergo catalytic reactions at low concentrations suggests that zinc release is a significant aspect of the therapeutic antioxidant actions of selenium compounds in antiinflammatory and anticarcinogenic agents.