Oxidative folding is an essential process for polypeptide chains containing cysteine (Cys) residues to form a bioactive three-dimensional structure. During this process, the folded state with the correct disulfide (SS) combination, which is found in the native state, cannot be obtained at 100% yield because various byproducts, such as misfolded states with mispaired SS bonds, oligomers, and aggregates are simultaneously produced. The formation of misfolded states in vivo has been suggested to cause critical human diseases such as neurodegenerative disorders. Therefore, the development of methods to promote the correct structural maturation of polypeptides, including Cys residues, both in vivo and in vitro, is a challenging task in protein synthesis, medicine, and drug discovery. To rapidly form correctly folded proteins at high yields, two potential strategies are available. First, called the outside strategy, is to control oxidative folding from the outside of proteins using artificial small molecules as catalyst and a reagent that mimics the function of protein disulfide isomerase, which catalyzes SS-related reactions during oxidative folding in cells. Second, called the inside strategy, is to insert mimics of SS linkage(s) into the inside of polypeptides to form a rigid covalent bond chemoselectively, thereby avoiding the formation of a misfolded state having mispaired SS bonds. In this review, recent developments and trends based on the unique redox properties of selenols and diselenides, which are selenium analogs of thiols and disulfides, respectively, are outlined, and their future prospects are discussed.
Selenoprotein P (SeP), encoded by the SELENOP gene, is the major selenium-containing protein in human plasma. SeP has 10 residues of selenocysteine (Sec, cysteine analog in which the sulfur is replaced by selenium), and Sec plays a significant role in the multifunctional properties of SeP. The one Sec residue on the N-terminal side functions for the redox reaction that reduces lipid hydroperoxides, while the 9 Sec residues on the C-terminal side are responsible for the selenium supplying activity. In the middle of SeP, the domain rich in basic amino acids containing consecutive histidine is present. SeP has been reported to have multiple metal-binding abilities such as Hg, Cd, Cu, Ni, Zn, and Co; however, its physiological significance and the effects on SeP functions remain unclear. In this review, the findings to date on the metal-binding properties of SeP and its structural relevance are summarized, particularly for methylmercury. The binding of other selenoproteins to metals is also described. Finally, the interactions of selenoproteins with various metals and its significance for biological defense are discussed.
The high toxicity of soluble selenium (Se) has led to the establishment of environmental standards in Japan. Consequently, various methods for recovering Se from wastewater and contaminated soil have been developed and applied. Despite the recovery and recycling potential of Se after wastewater and/or soil treatment, Se recycling has rarely been mentioned in previous studies. Therefore, a recycling method for Se proposed by the authors is outlined here. Briefly, the selenate contained in wastewater was converted into solid elemental Se or volatile dimethyl diselenide via Pseudomonas stutzeri NT-I metabolism, recovered, purified to high-purity elemental Se, and recycled. The advantages and disadvantages of this recycling method are discussed, as well as those of other recovery and recycling treatment. Overall, Se in soils and wastewater can be recovered by choosing a treatment method suitable for each condition and Se species.
Selenium plays vital roles as a defense against oxidative stress in the central nervous system. This essential micronutrient is transported to the brain in the form of selenoprotein P. Additionally, small molecular-mass selenium compounds are also suggested to participate in supplying selenium to the brain, although its definitive transport pathways to the brain still remain unclear. Selenotrisulfide (−S−Se−S−, STS) is a metabolic intermediate of selenium and can react with free cysteine (Cys) thiols in proteins through the thiol-exchange reaction (R−S−Se−S−R’ + R”−SH → R−S−Se−S−R” + R’−SH). These reactions of free Cys thiols in human hemoglobin (Hb) and serum albumin (HSA) with STS are involved in the selenium metabolic and/or transport pathway in red blood cells. In this study, rat dorsal root ganglion (DRG) neurons are supplemented with STS species including STSs bound to HSA and Hb to determine the selenium utilization efficiency from STS species. After incubation with STS species for 72 h, the cellular selenium concentration and activity of selenium-dependent glutathione peroxidase in DRG neurons increased as well as those incubated with selenious acid. Selenium from STS is thought to be absorbed and utilized for the selenoprotein synthesis in neurons.