Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603-8555, Japan.
Mol Microbiol. 2010 Jan;75(1):1-5. doi: 10.1111/j.1365-2958.2009.06953.x. Epub 2009 Nov 10.
The disulphide bond-introducing enzyme of bacteria, DsbA, sometimes oxidizes non-native cysteine pairs. DsbC should rearrange the resulting incorrect disulphide bonds into those with correct connectivity. DsbA and DsbC receive oxidizing and reducing equivalents, respectively, from respective redox components (quinones and NADPH) of the cell. Two mechanisms of disulphide bond rearrangement have been proposed. In the redox-neutral 'shuffling' mechanism, the nucleophilic cysteine in the DsbC active site forms a mixed disulphide with a substrate and induces disulphide shuffling within the substrate part of the enzyme-substrate complex, followed by resolution into a reduced enzyme and a disulphide-rearranged substrate. In the 'reduction-oxidation' mechanism, DsbC reduces those substrates with wrong disulphides so that DsbA can oxidize them again. In this issue of Molecular Microbiology, Berkmen and his collaborators show that a disulphide reductase, TrxP, from an anaerobic bacterium can substitute for DsbC in Escherichia coli. They propose that the reduction-oxidation mechanism of disulphide rearrangement can indeed operate in vivo. An implication of this work is that correcting errors in disulphide bonds can be coupled to cellular metabolism and is conceptually similar to the proofreading processes observed with numerous synthesis and maturation reactions of biological macromolecules.
细菌的二硫键引入酶 DsbA 有时会氧化非天然半胱氨酸对。DsbC 应该将由此产生的不正确的二硫键重新排列成具有正确连接性的二硫键。DsbA 和 DsbC 分别从细胞的各自氧化还原成分（醌和 NADPH）接收氧化和还原当量。已经提出了两种二硫键重排的机制。在氧化还原中性的“洗牌”机制中，DsbC 活性位点中的亲核半胱氨酸与底物形成混合二硫键，并在酶-底物复合物的底物部分诱导二硫键重排，随后解析为还原酶和二硫键重排的底物。在“还原-氧化”机制中，DsbC 还原那些具有错误二硫键的底物，以便 DsbA 可以再次氧化它们。在本期《分子微生物学》中，Berkmen 及其合作者表明，来自厌氧菌的二硫键还原酶 TrxP 可以在大肠杆菌中替代 DsbC。他们提出，二硫键重排的还原-氧化机制确实可以在体内起作用。这项工作的一个含义是，纠正二硫键中的错误可以与细胞代谢偶联，并且在概念上类似于观察到的许多生物大分子的合成和成熟反应中的校对过程。
