Nitric oxide (NO) is a highly diffusible molecule generated from a family of NO syntheses (NOSs) that convert L-arginine to L-citrulline using oxygen and NADPH. Under physiological conditions, NO is produced at low levels in response to endogenous stimuli such as acetylcholine and acts as critical messenger of intracellular signaling pathways. NO also has a variety of physiological functions such as neurotransmission, inflammatory reaction, vasodilation, and stimulates both angiogenesis and cell proliferation.
Protein S-nitrosylation is an NO-dependent reversible post-translational modification of cysteine that regulates both protein structure and function in bacteria, plants, and mammals. Over the past couple of decades, advanced proteomic approaches have led to the identification of more than a thousand S-nitrosylated (SNO-) proteins with diverse cellular functions. So far, we demonstrated that PDI, PTEN, and HDAC6 are targets of NO and regulate the enzymatic activity via S-nitrosylation.
Recently, we found a novel substrate of NO that is involved in the regulation of gene expression. In addition, we attempted to develop a specific inhibitor of S-nitrosylation of this substrate by the hierarchical virtual screening approaches. We will discuss those findings in this session.