protein nitrosylation

Definition

Target type: biologicalprocess

The covalent addition of a nitric oxide group to an amino acid within a protein. [GOC:ai, PMID:20972426]

Protein nitrosylation is a post-translational modification (PTM) that involves the covalent attachment of a nitric oxide (NO) molecule to a cysteine residue within a protein. This process is catalyzed by nitric oxide synthases (NOS) and is essential for a wide range of biological functions, including signal transduction, gene regulation, and cellular defense.

The nitrosylation process begins with the generation of NO by NOS enzymes. NO is a highly reactive molecule that readily reacts with cysteine residues in proteins to form S-nitrosothiols (SNOs). This reaction can occur directly, or it can be facilitated by various redox-active metal ions, such as iron or copper.

Once SNOs are formed, they can alter the conformation and function of proteins in several ways:

1. **Conformational Changes:** Nitrosylation can induce conformational changes in proteins by altering the redox state of cysteine residues, which can disrupt protein-protein interactions and affect enzyme activity.

2. **Redox Signaling:** SNOs can act as redox signaling molecules, mediating the transmission of redox signals within cells and influencing downstream cellular processes.

3. **Protein Degradation:** Nitrosylation can target proteins for degradation by promoting their ubiquitination and subsequent proteasomal degradation.

4. **Enzyme Activation or Inhibition:** Nitrosylation can activate or inhibit the activity of enzymes by affecting their catalytic sites or by altering their interactions with substrates or cofactors.

The biological consequences of protein nitrosylation are diverse and context-dependent. It plays a critical role in various physiological processes, including:

- **Cardiovascular Regulation:** Nitrosylation regulates vascular tone, blood pressure, and platelet aggregation.

- **Neurotransmission:** Nitrosylation modulates neurotransmitter release, neuronal plasticity, and synaptic signaling.

- **Immune Response:** Nitrosylation regulates immune cell function, including cytokine production and leukocyte activation.

- **Cellular Defense:** Nitrosylation is involved in cellular defense against oxidative stress and pathogens.

- **Metabolic Regulation:** Nitrosylation regulates glucose metabolism, insulin signaling, and lipid homeostasis.

However, dysregulation of nitrosylation can lead to various pathological conditions, including:

- **Cardiovascular Disease:** Nitrosylation imbalance contributes to atherosclerosis, hypertension, and heart failure.

- **Neurodegenerative Diseases:** Nitrosylation is implicated in the pathogenesis of Alzheimer's disease, Parkinson's disease, and stroke.

- **Cancer:** Nitrosylation can promote tumor growth and metastasis by altering cell signaling pathways.

- **Inflammatory Disorders:** Nitrosylation contributes to inflammation by modulating the activity of inflammatory mediators.

In summary, protein nitrosylation is a critical PTM that plays a diverse and multifaceted role in cellular function and disease. Further research is ongoing to elucidate the precise mechanisms of nitrosylation and its implications in various physiological and pathological processes.'
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Proteins (1)

Compounds (1)