S-Nitrosothiol Chemistry at the Single-Molecule Level

摘要

Nitric oxide (NO) and its relatives (notably RSNO and HNO) perform important roles as regulatory molecules in health and disease.NO activates guanylate cyclase by binding to its ferrous heme (see the Supporting Information, Figure S1). The lifetime of NO is short, being milliseconds to seconds, and therefore it is unlikely that NO diffuses more than approximately 100 um, which is in the range of a few cells, from the site at which it is generated. Through poorly understood mechanisms, NO is also converted in vivo into small molecule and protein S-nitrosothiols (RSNOs). RSNOs modulate cellular activity in ways that differ from the direct action of NO. Furthermore, RSNO derivatives of albumin and hemoglobin are sufficiently long-lived to be transported in the circulation. In addition, NO is passed from one thiol to another by transnitrosation, which can be facilitated by specific protein-protein interactions, and protein function can be modulated by S nitrosation. Protein SNOs are also converted into other derivatives, such as S-glutathionylated proteins, thus generating a complex signaling web (Figure S1). RSNO also act as a source of HNO (nitroxyl), which is also a locally acting regulatory molecule with biological effects that differ from and even oppose those of NO .