Ortenberg Ron, Beckwith Jon
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Antioxid Redox Signal. 2003 Aug;5(4):403-11. doi: 10.1089/152308603768295140.
A large family of enzymes contributes to the thiol-disulfide redox environment of the cells of most organisms. These proteins belong to pathways that carry out a variety of reactions, including the promotion of disulfide bond formation in extracytoplasmic proteins, the isomerization of proteins with incorrect disulfide bonds, and the reduction of disulfide bonds in the active sites of cytoplasmic proteins. Although the redox activities of these proteins measured in vitro often is consistent with the role (oxidant or reductant) these proteins perform in vivo, this is not always the case. The measured redox potentials can even suggest a function for a protein opposite of that which it carries out in the cell. Structural features of such proteins can contribute to a direction of electron transfer inconsistent with the redox potential. Furthermore, the environment in which such proteins are found may determine the protein's physiological role. Detailed analysis of these proteins in Escherichia coli provides strains that are useful for biotechnological purposes. Increasing the activity of certain of these proteins in the cell envelope or altering the thiol-disulfide redox environment of the cytoplasm to make it more oxidizing enhances the yield of useful disulfide bond-containing proteins such as tissue plasminogen activator and immunoglobulins.
一大类酶对大多数生物体细胞的硫醇-二硫键氧化还原环境有影响。这些蛋白质属于执行各种反应的途径,包括促进胞外蛋白质中二硫键的形成、使具有错误二硫键的蛋白质异构化以及还原胞质蛋白质活性位点中的二硫键。尽管在体外测量的这些蛋白质的氧化还原活性通常与它们在体内执行的作用(氧化剂或还原剂)一致,但情况并非总是如此。测得的氧化还原电位甚至可能表明一种蛋白质的功能与其在细胞中执行的功能相反。此类蛋白质的结构特征可能导致电子转移方向与氧化还原电位不一致。此外,发现此类蛋白质的环境可能决定其生理作用。对大肠杆菌中这些蛋白质的详细分析提供了对生物技术有用的菌株。提高某些此类蛋白质在细胞膜中的活性或改变细胞质的硫醇-二硫键氧化还原环境使其更具氧化性,可提高有用的含二硫键蛋白质(如组织纤溶酶原激活剂和免疫球蛋白)的产量。