peptidyl-cysteine S-trans-nitrosylation

Definition

Target type: biologicalprocess

Transfer of a nitric oxide (NO) group from one cysteine residue to another. [PMID:19854201, PMID:20972425, PMID:20972426]

Peptidyl-cysteine S-trans-nitrosylation is a post-translational modification where nitric oxide (NO) reacts with a cysteine residue in a protein, forming an S-nitrosothiol (SNO) group. This process is crucial for regulating various cellular functions, including signaling, gene expression, and redox homeostasis.

Here's a detailed breakdown of the process:

1. **NO Generation:** NO is produced by nitric oxide synthase (NOS) enzymes, which catalyze the oxidation of L-arginine to L-citrulline and NO.

2. **NO Diffusion:** NO is a highly diffusible molecule that can readily cross cell membranes. It can then interact with various targets, including cysteine residues in proteins.

3. **S-Nitrosylation Reaction:** The reaction of NO with a cysteine residue involves a two-step process. First, NO reacts with a reactive oxygen species (ROS) like superoxide (O2-) to form peroxynitrite (ONOO-). Peroxynitrite can then directly nitrosylate cysteine residues, forming an SNO group. Alternatively, NO can react with a thiolate anion (RS-) on a cysteine residue, forming an SNO group.

4. **SNO Formation:** The resulting SNO group is a covalent modification that can alter the protein's structure, function, and interactions.

5. **Regulation of Protein Function:** S-nitrosylation can modulate protein activity in various ways, including:
* **Altering protein conformation:** The bulky SNO group can induce conformational changes, affecting protein folding and stability.
* **Modifying enzymatic activity:** S-nitrosylation can either activate or inhibit enzyme activity by affecting substrate binding or catalytic site accessibility.
* **Changing protein-protein interactions:** SNO groups can alter the binding affinity of proteins to other molecules, influencing signaling pathways and cellular processes.

6. **De-nitrosylation:** The SNO group can be removed by denitrosylase enzymes, restoring the cysteine residue to its native state. De-nitrosylation is essential for regulating the duration and specificity of S-nitrosylation.

7. **Biological Significance:** Peptidyl-cysteine S-trans-nitrosylation plays a vital role in various biological processes, including:
* **Cardiovascular system:** NO regulates vascular tone and blood pressure by modulating smooth muscle relaxation.
* **Nervous system:** NO is involved in synaptic plasticity, neurotransmission, and memory formation.
* **Immune system:** NO participates in immune responses by regulating immune cell activation and cytokine production.
* **Cellular signaling:** S-nitrosylation is a crucial signaling mechanism that mediates diverse cellular responses to stimuli.

8. **Pathological Implications:** Dysregulation of S-nitrosylation has been implicated in various diseases, including:
* **Cardiovascular disease:** Imbalances in NO signaling contribute to atherosclerosis, hypertension, and heart failure.
* **Neurodegenerative diseases:** Altered S-nitrosylation patterns are associated with Alzheimer's disease and Parkinson's disease.
* **Cancer:** S-nitrosylation can regulate tumor growth, angiogenesis, and metastasis.

In summary, peptidyl-cysteine S-trans-nitrosylation is a crucial post-translational modification that plays a fundamental role in regulating cellular function and signaling. This process involves the reversible formation of SNO groups on cysteine residues, impacting protein conformation, activity, and interactions. Dysregulation of S-nitrosylation can contribute to various diseases, highlighting its importance in maintaining cellular homeostasis.'
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Proteins (1)

Compounds (18)