Laboratory of Protein Crystallography and Structural Biology, IFSC-USP, Av. Trabalhador Sao Carlense 400, P.O. Box: 369, CEP 13560-970, Sao Carlos/SP, Brazil.
Curr Med Chem. 2014;21(15):1772-80. doi: 10.2174/0929867320666131119121108.
Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms. Although several functions have been attributed to this class, the majority of the proteins are involved in oxidative stress defense. Here, we discuss the kinetoplastid selenocysteine pathway and how selenium supplementation is able to alter the infection course of trypanosomatids in detail. These organisms possess the canonical elements required for selenoprotein production such as phosphoseryl tRNA kinase (PSTK), selenocysteine synthase (SepSecS), selenophosphase synthase (SelD or SPS), and elongation factor EFSec (SelB), whereas other important factors presented in mammal cells, such as SECIS binding protein 2 (SBP) and SecP 43, are absent. The selenoproteome of trypanosomatids is small, as is the selenoproteome of others parasites, which is in contrast to the large number of selenoproteins found in bacteria, aquatic organisms and higher eukaryotes. Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage. New experiments are necessary to determine how selenium acts, but evidence suggests that immune response modulation and increased host defense against oxidative stress contribute to control of the parasite infection.
硒（Se）是几种生物体必需的微量元素，存在于蛋白质中的硒代半胱氨酸（Sec 或 U）中，该氨基酸通过单个原子（分别为 Se 而不是 O 或 S）在化学上与丝氨酸和半胱氨酸不同。Sec 通过称为硒代半胱氨酸掺入序列（SECIS）的 mRNA 茎环结构在框架内 UGA 密码子处掺入硒蛋白，SECIS 存在于硒蛋白 mRNA 中和特定的硒代半胱氨酸合成和掺入机制中。硒蛋白存在于所有领域，但并非存在于所有生物体中。尽管已经赋予了该类许多功能，但大多数蛋白质都参与了氧化应激防御。在这里，我们详细讨论了动基体硒代半胱氨酸途径，以及硒补充剂如何改变锥虫的感染过程。这些生物体具有产生硒蛋白所需的典型元件，例如磷酸丝氨酸 tRNA 激酶（PSTK）、硒代半胱氨酸合酶（SepSecS）、硒磷酸酶合酶（SelD 或 SPS）和延伸因子 EFSec（SelB），而在哺乳动物细胞中存在的其他重要因素，例如 SECIS 结合蛋白 2（SBP）和 SecP 43，则不存在。锥虫的硒蛋白组很小，其他寄生虫的硒蛋白组也很小，与细菌、水生生物和高等真核生物中发现的大量硒蛋白形成对比。锥虫和利什曼原虫对金诺芬（一种有效的硒蛋白抑制剂）敏感；然而，可能的药物机制与动基体中的硒蛋白无关。硒补充剂可降低各种锥虫感染的寄生虫血症，并降低与贫血和寄生虫引起的器官损伤等疾病相关的重要参数。需要进行新的实验以确定硒的作用方式，但有证据表明，免疫反应调节和增加宿主对氧化应激的防御有助于控制寄生虫感染。
