Active sites of thioredoxin reductases:: Why selenoproteins?
Active sites of thioredoxin reductases:: Why selenoproteins?
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DOI：
10.1073/pnas.2134510100
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发表时间：
2003-10-28
影响因子：
11.1
通讯作者：
Arnér, ESJ
中科院分区：
文献类型：
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作者：
Gromer, S;Johansson, L;Arnér, ESJ
硒是哺乳动物必需的微量元素，作为硒半胱氨酸被纳入选定的一类硒蛋白中。所有已知的哺乳动物硫氧还蛋白（Trx）还原酶（TrxRs）的c端氧化还原中心-Gly-Cys-Sec-Gly-COOH都使用硒来还原Trx和其他底物，而果蝇TrxR的相应序列是-Ser-Cys-Cys-Ser-COOH。令人惊讶的是，这些同源酶的催化能力是相似的，而直接将哺乳动物的TrxR或其他硒酶sec替换为cys，则产生几乎无活性的酶。因此，TrxRs是比较酶学研究硒代半胱氨酸生物学的理想选择。本研究表明，果蝇TrxR的c端Cys残基两侧的丝氨酸残基负责激活半胱氨酸，以匹配哺乳动物TrxR中硒型半胱氨酸-半胱氨酸对的催化效率，从而消除了对硒的需求。这一发现表明，硒酶的出现，这意味着生物体是硒依赖的，并不一定与酶效率的提高有关。我们的数据表明，硒酶的选择优势是在更广泛的底物和更广泛的微环境条件下，酶的活性是可能的。
Selenium, an essential trace element for mammals, is incorporated into a selected class of selenoproteins as selenocysteine. All known isoenzymes of mammalian thioredoxin (Trx) reductases (TrxRs) employ selenium in the C-terminal redox center -Gly-Cys-Sec-Gly-COOH for reduction of Trx and other substrates, whereas the corresponding sequence in Drosophila melanogaster TrxR is -Ser-Cys-Cys-Ser-COOH. Surprisingly, the catalytic competence of these orthologous enzymes is similar, whereas direct Sec-to-Cys substitution of mammalian TrxR, or other selenoenzymes, yields almost inactive enzyme. TrxRs are therefore ideal for studying the biology of selenocysteine by comparative enzymology. Here we show that the serine residues flanking the C-terminal Cys residues of Drosophila TrxRs are responsible for activating the cysteines to match the catalytic efficiency of a selenocysteine-cysteine pair as in mammalian TrxR, obviating the need for selenium. This finding suggests that the occurrence of selenoenzymes, which implies that the organism is selenium-dependent, is not necessarily associated with improved enzyme efficiency. Our data suggest that the selective advantage of selenoenzymes is a broader range of substrates and a broader range of microenvironmental conditions in which enzyme activity is possible.