Redox-sensitive proteins susceptible to S-nitrosylation (SNO-proteins)

Redox-sensitive proteins susceptible to S-nitrosylation represent a diverse group of proteins whose function, stability, and localization are regulated by the covalent attachment of a nitric oxide (NO) moiety to specific cysteine thiol groups [1.3.1, 1.3.5]. This post-translational modification, known as S-nitrosylation, acts as a molecular switch similar to phosphorylation, mediating a significant portion of NO's biological activity across various organ systems [1.3.2, 1.3.4]. Key targets within this class include enzymes like GAPDH and Caspase-3, receptors such as the NMDA receptor, and ion channels like the Ryanodine receptor [1.3.3, 1.4.1]. Dysregulation of the "S-nitrosoproteome"—either through excessive S-nitrosylation (nitrosative stress) or insufficient denitrosylation—is implicated in the pathogenesis of numerous conditions, including neurodegenerative diseases like Parkinson's and Alzheimer's, cardiovascular disorders, and cancer [1.3.2, 1.3.3]. Therapeutic strategies involve the use of NO donors to restore signaling or inhibitors of denitrosylases, such as S-nitrosoglutathione reductase (GSNOR), to maintain S-nitrosothiol levels [1.2.1, 1.3.2]. Recent advancements focus on "targeted S-nitrosylation" using small molecules like NMT5 to improve selectivity and reduce off-target effects [1.2.1]. However, a major challenge in targeting these proteins is the potential for non-specific nitrosylation, which can lead to systemic hypotension and oxidative damage [1.2.1, 1.4.2]. Monitoring S-nitrosothiol levels in biological fluids is currently being explored as a biomarker for disease progression and therapeutic efficacy [1.1.1, 1.3.3].

Other names

S-nitrosylated proteinsS-nitrosoproteomeNitrosothiolsS-nitrosothiolsSNO-modified proteins

Drugs targeting this class primarily act as nitric oxide (NO) donors, which facilitate the covalent attachment of NO to cysteine thiols (S-nitrosylation), or as inhibitors of denitrosylases like GSNOR to prevent the removal of these modifications [1.2.1, 1.3.2].