Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease.
Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease.
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DOI：
10.1007/s00109-012-0878-z
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Stamler, Jonathan S.
中科院分区：
文献类型：
--
作者：
Anand, Puneet;Stamler, Jonathan S.
关键词：
一氧化氮主要通过蛋白质内变构和活性部位半胱氨酸硫醇的s -亚硝基化，形成s -亚硝基蛋白（sno -protein）参与细胞信号转导。蛋白质的s -亚硝基化已被证明影响广泛的功能参数，包括酶活性、亚细胞定位、蛋白质-蛋白质相互作用和蛋白质稳定性。类似于其他普遍存在的由酶调控的翻译后修饰，包括磷酸化和泛素化，越来越多的证据表明存在调节蛋白质s -亚硝基化的酶机制。特别是，研究已经确定了多种酶（亚硝基化酶和脱硝基化酶），这些酶在生理环境下参与蛋白质的靶向s -亚硝基化或脱硝基化。亚硝基化是指sno蛋白将NO基团转移到受体蛋白（Cys-to-Cys转移）的转亚硝基化，但也存在由金属蛋白催化的转亚硝基化（Metal-to-Cys转移）。相反，脱亚硝基化酶从sno蛋白中去除NO基团，最终使用来自NADH或NADPH的还原等价物。在这里，我们关注最近发现的亚硝基酶和反硝基酶，以及它们的异常活动可能在健康和疾病中发挥作用的概念。
Nitric oxide participates in cellular signal transduction largely through S-nitrosylation of allosteric and active-site cysteine thiols within proteins, forming S-nitrosoproteins (SNO-proteins). S-nitrosylation of proteins has been demonstrated to affect a broad range of functional parameters including enzymatic activity, subcellular localization, protein–protein interactions, and protein stability. Analogous to other ubiquitous posttranslational modifications that are regulated enzymatically, including phosphorylation and ubiquitinylation, accumulating evidence suggests the existence of enzymatic mechanisms for regulating protein S-nitrosylation. In particular, studies have led to the identification of multiple enzymes (nitrosylases and denitrosylases) that participate in targeted S-nitrosylation or denitrosylation of proteins in physiological settings. Nitrosylases are best characterized in the context of transnitrosylation in which a SNO-protein transfers an NO group to an acceptor protein (Cys-to-Cys transfer), but examples of transnitrosylation catalyzed by metalloproteins (Metal-to-Cys transfer) also exist. By contrast, denitrosylases remove the NO group from SNO-proteins, ultimately using reducing equivalents derived from NADH or NADPH. Here, we focus on the recent discoveries of nitrosylases and denitrosylases and the notion that their aberrant activities may play roles in health and disease.
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