Structure of an S–nitrosothiol. R denotes some organic group.
In
organic chemistry, S-nitrosothiols, also known as thionitrites, are
organic compounds or
functional groups containing a
nitroso group attached to the
sulfur atom of a
thiol.[1]S-Nitrosothiols have the general formula R−S−N=O, where R denotes an organic group. Originally suggested by
Ignarro to serve as intermediates in the action of organic nitrates, endogenous S-nitrosothiols were discovered by
Stamler and colleagues (S-nitrosoalbumin in plasma and
S-nitrosoglutathione in airway lining fluid) and shown to represent a main source of NO bioactivity in vivo. More recently, S-nitrosothiols have been implicated as primary mediators of protein
S-nitrosylation, the oxidative modification of
cysteine thiol that provides ubiquitous regulation of protein function.
S-Nitrosothiols have received much attention in
biochemistry because they serve as donors of both the
nitrosonium ion NO+ and of
nitric oxide and thus best rationalize the chemistry of NO-based signaling in living systems, especially related to
vasodilation.[2]Red blood cells, for instance, carry an essential reservoir of S-nitrosohemoglobin and release S-nitrosothiols into the bloodstream under low-oxygen conditions, causing the blood vessels to dilate.[3]
S-nitrosothiols are composed of small molecules, peptides and proteins. The addition of a nitroso group to a sulfur atom of an
amino acid residue of a protein is known as S-nitrosylation or S-
nitrosation. This is a reversible process and a major form of
posttranslational modification of proteins.[4]
S-Nitrosylated proteins (SNO-proteins) serve to transmit
nitric oxide (NO) bioactivity and to regulate protein function through enzymatic mechanisms analogous to phosphorylation and ubiquitinylation: SNO donors target specific amino acids motifs; post-translational modification leads to changes in protein activity, protein interactions, or subcellular location of target proteins; all major classes of proteins can undergo S-nitrosylation, which is mediated by enzymes that add (nitrosylases) and remove (denitrosylases) SNO from proteins, respectively. Accordingly, nitric oxide synthase (NOS) activity does not directly lead to SNO formation, but rather requires an additional class of enzymes (SNO synthases), which catalyze denovo S-nitrosylation. NOSs ultimately target specific Cys residues for S-nitrosylation through conjoint actions of SNO-synthases and transnitrosylases (transnitrosation reactions), which are involved in virtually all forms of cell signaling, ranging from regulation of ion channels and G-protein coupled reactions to receptor stimulation and activation of nuclear regulatory protein.[5][6]
Structure and reactions
The prefix "S" indicates that the NO group is attached to sulfur. The S-N-O angle is near 114°, reflecting the influence of the
lone pair of electrons on nitrogen.[7]
^Arulsamy, N.; Bohle, D. S.; Butt, J. A.; Irvine, G. J.; Jordan, P. A.; Sagan, E. (1999). "Interrelationships between Conformational Dynamics and the Redox Chemistry of S-Nitrosothiols". Journal of the American Chemical Society. 121 (30): 7115–7123.
doi:
10.1021/ja9901314.
^Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. (2002). "Nitric Oxide Donors: Chemical Activities and Biological Applications". Chemical Reviews. 102 (4): 1091–1134.
doi:
10.1021/cr000040l.
PMID11942788.
^Goto, K.; Hino, Y.; Kawashima, T.; Kaminaga, M.; Yano, E.; Yamamoto, G.; Takagi, N.; Nagase, S. (2000). "Synthesis and crystal structure of a stable S-nitrosothiol bearing a novel steric protection group and of the corresponding S-nitrothiol". Tetrahedron Letters. 41 (44): 8479–8483.
doi:
10.1016/S0040-4039(00)01487-8.