S-nitroso proteome of Mycobacterium tuberculosis:: Enzymes of intermediary metabolism and antioxidant defense
S-nitroso proteome of Mycobacterium tuberculosis:: Enzymes of intermediary metabolism and antioxidant defense
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DOI：
10.1073/pnas.0406133102
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发表时间：
2005-01-11
影响因子：
11.1
通讯作者：
Nathan, CF
中科院分区：
文献类型：
--
作者：
Rhee, KY;Erdjument-Bromage, H;Nathan, CF
对结核分枝杆菌 (Mtb) 的免疫反应包括一氧化氮 (NO) 合酶 (NOS)2 的表达，其产物可以在体外杀死 Mtb，其摩尔效力大于许多传统抗结核药物。然而，结核分枝杆菌中活性氮中间体（RNI）的作用靶点尚不清楚。 RNI 的一项主要作用是蛋白质 S-亚硝基化。在这里，据我们所知，我们描述了用杀菌浓度的 RNI 处理 Mtb 后整个生物体中 S-亚硝基化的首次蛋白质组学分析。已鉴定的 29 种 S-亚硝基蛋白都是酶，主要服务于中间代谢、脂质代谢和/或抗氧化防御。许多是必不可少的或与毒力有关，包括对 RNI 的防御。对于所测试的两种目标酶（硫辛酰胺脱氢酶和分枝杆菌蛋白酶体 ATP 酶）中的每一种，S-亚硝基化都会导致酶抑制。此外，内源性生物素化蛋白质被驱动成混合二硫键复合物。通过蛋白质 S-亚硝基化和混合二硫键作用来靶向代谢酶和抗氧化防御可能有助于 RNI 的抗分枝杆菌 I 作用。
The immune response to Mycobacterium tuberculosis (Mtb) includes expression of nitric oxide (NO) synthase (NOS)2, whose products can kill Mtb in vitro with a molar potency greater than that of many conventional antitubercular agents. However, the targets of reactive nitrogen intermediates (RNIs) in Mtb are unknown. One major action of RNIs is protein S-nitrosylation. Here, we describe, to our knowledge, the first proteomic analysis of S-nitrosylation in a whole organism after treating Mtb with bactericidal concentrations of RNIs. The 29 S-nitroso proteins identified are all enzymes, mostly serving intermediary metabolism, lipid metabolism, and/or antioxidant defense. Many are essential or implicated in virulence, including defense against RNIs. For each of two target enzymes tested, lipoamide dehydrogenase and mycobacterial proteasome ATPase, S-nitrosylation caused enzyme inhibition. Moreover, endogenously biotinylated proteins were driven into mixed disulfide complexes. Targeting of metabolic enzymes and antioxidant defenses by means of protein S-nitrosylation and mixed disulfide bonding may contribute to the anti mycobacteria I actions of RNIs.