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S-nitrosylation signaling

Author and Curator: Larry H Bernstein, MD, FCAP

S-nitrosylation signaling in cell biology.

Gaston BM¹, Carver J, Doctor A, Palmer LA

Mol Interv. 2003 Aug; 3(5): 253-63  PMID: 14993439

S-Nitrosylated proteins form

1. when a cysteine thiol reacts with nitric oxide (NO) in the presence of an electron acceptor to form an S-NO bond.
2. Under physiological conditions, this posttranslational modification affects the function a wide array of cell proteins, ranging from ion channels to nuclear regulatory proteins.

Recent evidence suggests that

1) S-nitrosylated proteins can be synthesized by exposure of specific redox-active motifs to NO,

• through transnitrosation/transfer reactions, or
• through metalloprotein-catalyzed reactions;

2) S-nitrosothiols can be sequestered in

• membranes,
• lipophilic protein folds, or
• in vesicles to preserve their activity; and

3) S-nitrosothiols can be degraded by a number of enzymes systems.

These recent insights regarding the

1. bioactivities,
2. molecular signaling pathways, and
3. metabolism of endogenous S-nitrosothiols

have suggested several new therapies for disease ranging from cystic fibrosis to pulmonary hypertension.

Key pathways involving NO