Department of Microbiology, University of Georgia, Athens, GA 30602, USA.
Biochem J. 2013 Feb 15;450(1):141-8. doi: 10.1042/BJ20121434.
The persistence of the gastric pathogen Helicobacter pylori is due in part to urease and Msr (methionine sulfoxide reductase). Upon exposure to relatively mild (21% partial pressure of O2) oxidative stress, a Δmsr mutant showed both decreased urease specific activity in cell-free extracts and decreased nickel associated with the partially purified urease fraction as compared with the parent strain, yet urease apoprotein levels were the same for the Δmsr and wild-type extracts. Urease activity of the Δmsr mutant was not significantly different from the wild-type upon non-stress microaerobic incubation of strains. Urease maturation occurs through nickel mobilization via a suite of known accessory proteins, one being the GTPase UreG. Treatment of UreG with H2O2 resulted in oxidation of MS-identified methionine residues and loss of up to 70% of its GTPase activity. Incubation of pure H2O2-treated UreG with Msr led to reductive repair of nine methionine residues and recovery of up to full enzyme activity. Binding of Msr to both oxidized and non-oxidized UreG was observed by cross-linking. Therefore we conclude Msr aids the survival of H. pylori in part by ensuring continual UreG-mediated urease maturation under stress conditions.
幽门螺杆菌（Helicobacter pylori）这种胃部病原体之所以能够持续存在，部分原因是由于其脲酶（urease）和 Msr（甲硫氨酸亚砜还原酶）。在接触相对温和的（21%的氧气分压）氧化应激时，与亲本株相比，Δmsr 突变体的细胞游离提取物中的脲酶比活和与部分纯化的脲酶级分相关的镍均降低，但 Δmsr 和野生型提取物中的脲酶脱辅基蛋白水平相同。在非应激微需氧孵育条件下，与野生型相比，Δmsr 突变体的脲酶活性没有明显差异。脲酶的成熟是通过一系列已知的辅助蛋白（一种是 GTPase UreG）来实现镍的动员。用 H2O2 处理 UreG 会导致 MS 鉴定的蛋氨酸残基氧化，并丧失其高达 70%的 GTP 酶活性。将纯 H2O2 处理的 UreG 与 Msr 孵育可导致九个蛋氨酸残基的还原修复，并使酶活性恢复至全酶活性。交联实验观察到 Msr 与氧化和非氧化的 UreG 结合。因此，我们得出结论，Msr 通过确保在应激条件下持续进行 UreG 介导的脲酶成熟，从而在一定程度上帮助 H. pylori 的存活。
