Rietsch A, Beckwith J
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Annu Rev Genet. 1998;32:163-84. doi: 10.1146/annurev.genet.32.1.163.
Disulfide bonds are required for the stability and function of a large number of proteins. Genetic analysis in combination with biochemical studies have elucidated the main catalysts involved in facilitating these processes in the cell. All enzymes involved in thiol-disulfide metabolism have a conserved active site that consists of two cysteine residues, separated by two intervening amino acids, the Cys-Xaa-Xaa-Cys motif. While these enzymes are capable of catalyzing both disulfide bond formation and reduction, they have evolved to perform one or the other reaction more efficiently. In the cytoplasm, multiple pathways are involved in the reduction of disulfide bonds that occur as part of the catalytic cycle of a variety of metabolic enzymes. In the bacterial periplasm, a system for the efficient introduction as well as isomerization of disulfide bonds is in place. In eukaryotes, disulfide bonds are introduced into proteins in the endoplasmic reticulum. Genetic studies have recently begun to reveal new features of this process. While the enzyme mechanisms of thiol-disulfide oxidoreductases have been the subject of much scrutiny, questions remain regarding where and when they act in vivo, their specificities, and the maintenance of the redox environment that determines their function.
二硫键对于大量蛋白质的稳定性和功能至关重要。遗传分析与生化研究相结合，阐明了细胞中促进这些过程的主要催化剂。所有参与硫醇 - 二硫代谢的酶都有一个保守的活性位点，该位点由两个半胱氨酸残基组成，中间间隔两个氨基酸，即Cys-Xaa-Xaa-Cys基序。虽然这些酶能够催化二硫键的形成和还原，但它们已经进化为更有效地进行其中一种反应。在细胞质中，多种途径参与了作为各种代谢酶催化循环一部分而出现的二硫键的还原。在细菌周质中，存在一个用于二硫键高效引入以及异构化的系统。在真核生物中，二硫键在内质网中被引入蛋白质。遗传研究最近开始揭示这一过程的新特征。虽然硫醇 - 二硫氧化还原酶的酶机制受到了广泛的审查，但关于它们在体内的作用位置和时间、它们的特异性以及决定其功能的氧化还原环境的维持等问题仍然存在。
