National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, South Korea.
J Biol Chem. 2012 Dec 14;287(51):42516-24. doi: 10.1074/jbc.M112.421214. Epub 2012 Oct 24.
Peroxiredoxins (Prxs) are ubiquitous antioxidant enzymes reducing toxic peroxides. Two distinct 2-Cys Prxs, Prx1 and Prx2, were identified in Vibrio vulnificus, a facultative aerobic pathogen. Both Prxs have two conserved catalytic cysteines, C(P) and C(R), but Prx2 is more homologous in amino acid sequences to eukaryotic Prx than to Prx1. Prx2 utilized thioredoxin A as a reductant, whereas Prx1 required AhpF. Prx2 contained GGIG and FL motifs similar to the motifs conserved in sensitive Prxs and exhibited sensitivity to overoxidation. MS analysis and C(P)-SO(3)H specific immunoblotting demonstrated overoxidation of C(P) to C(P)-SO(2)H (or C(P)-SO(3)H) in vitro and in vivo, respectively. In contrast, Prx1 was robust and C(P) was not overoxidized. Discrete expression of the Prxs implied that Prx2 is induced by trace amounts of H(2)O(2) and thereby residential in cells grown aerobically. In contrast, Prx1 was occasionally expressed only in cells exposed to high levels of H(2)O(2). A mutagenesis study indicated that lack of Prx2 accumulated sufficient H(2)O(2) to induce Prx1. Kinetic properties indicated that Prx2 effectively scavenges low levels of peroxides because of its high affinity to H(2)O(2), whereas Prx1 quickly degrades higher levels of peroxides because of its high turnover rate and more efficient reactivation. This study revealed that the two Prxs are differentially optimized for detoxifying distinct ranges of H(2)O(2), and proposed that Prx2 is a residential scavenger of peroxides endogenously generated, whereas Prx1 is an occasional scavenger of peroxides exogenously encountered. Furthermore, genome sequence database search predicted widespread coexistence of the two Prxs among bacteria.
过氧化物酶(Prxs)是普遍存在的抗氧化酶,可以还原有毒的过氧化物。在兼性需氧病原体副溶血性弧菌中鉴定出两种不同的 2-Cys Prxs,Prx1 和 Prx2。两种 Prx 都有两个保守的催化半胱氨酸 C(P)和 C(R),但 Prx2 在氨基酸序列上与真核 Prx 比 Prx1 更同源。Prx2 将硫氧还蛋白 A 用作还原剂,而 Prx1 需要 AhpF。Prx2 含有 GGIG 和 FL 基序,与敏感 Prxs 中保守的基序相似,并表现出对过氧化物的敏感性。MS 分析和 C(P)-SO(3)H 特异性免疫印迹表明,C(P)在体外和体内分别过氧化为 C(P)-SO(2)H(或 C(P)-SO(3)H)。相比之下,Prx1 稳定且 C(P)不过氧化。Prxs 的离散表达表明,Prx2 是由痕量 H(2)O(2)诱导的,因此在需氧生长的细胞中存在。相反,Prx1 仅在暴露于高浓度 H(2)O(2)的细胞中偶尔表达。诱变研究表明,缺乏 Prx2 会积累足够的 H(2)O(2)来诱导 Prx1。动力学特性表明,由于其对 H(2)O(2)的高亲和力,Prx2 可以有效地清除低水平的过氧化物,而由于其高周转率和更有效的再激活,Prx1 可以快速降解更高水平的过氧化物。这项研究表明,这两种 Prxs 针对不同范围的 H(2)O(2)进行了差异化优化,提出 Prx2 是内源性产生的过氧化物的常驻清除剂,而 Prx1 是外源性遇到的过氧化物的偶发清除剂。此外,基因组序列数据库搜索预测了这两种 Prxs 在细菌中的广泛共存。