protein sulfhydration

Definition

Target type: biologicalprocess

The modification of a protein amino acid by the addition of sulfur. [GOC:jl, GOC:jsg, PMID:19903941, PMID:22169477, PMID:8161529]

Protein sulfhydration is a post-translational modification (PTM) that involves the covalent attachment of a sulfur atom to a cysteine residue in a protein. This process plays a crucial role in regulating protein function, cellular signaling, and redox homeostasis. The sulfur atom is typically derived from hydrogen sulfide (H2S), a gasotransmitter that acts as a signaling molecule in various biological systems.

The sulfhydration process involves a two-step mechanism:

1. **Thiolate Anion Formation:** Cysteine residues in proteins can deprotonate to form thiolate anions (RS-), which are highly nucleophilic.
2. **Sulfur Atom Transfer:** The thiolate anion reacts with H2S or other sulfur donors, leading to the formation of a persulfide bond (RSSH) between the sulfur atom and the cysteine residue.

The persulfide bond is a reversible modification, and its formation and removal are tightly regulated by cellular enzymes and redox conditions. Several enzymes are involved in the sulfhydration process, including:

* **CBS (cystathionine beta-synthase)**: This enzyme catalyzes the production of H2S from cysteine.
* **CSE (cystathionine gamma-lyase)**: This enzyme also produces H2S from cysteine.
* **3MST (3-mercaptopyruvate sulfurtransferase)**: This enzyme transfers sulfur atoms from 3-mercaptopyruvate to cysteine residues.

Sulfhydration can have significant effects on protein function, including:

* **Altering protein conformation and stability:** The addition of a sulfur atom can modify the local structure and stability of a protein.
* **Modifying protein-protein interactions:** Sulfhydration can modulate the interactions between proteins, leading to changes in signaling pathways and cellular processes.
* **Regulating enzyme activity:** Sulfhydration can activate or inhibit the activity of enzymes by affecting their catalytic sites or binding to regulatory domains.

Sulfhydration is involved in a wide range of physiological processes, including:

* **Cardiovascular regulation:** Sulfhydration plays a role in regulating vascular tone and blood pressure.
* **Neuroprotection:** Sulfhydration protects neurons against oxidative stress and neurodegenerative diseases.
* **Immune responses:** Sulfhydration modulates immune cell function and inflammatory responses.
* **Metabolism:** Sulfhydration is involved in regulating glucose metabolism and lipid metabolism.

Dysregulation of sulfhydration has been implicated in various pathological conditions, including:

* **Cardiovascular diseases:** Abnormal sulfhydration is associated with heart failure, stroke, and atherosclerosis.
* **Neurological disorders:** Dysfunctional sulfhydration contributes to Alzheimer's disease, Parkinson's disease, and stroke.
* **Cancer:** Sulfhydration can promote tumor growth and metastasis.

Further research is needed to fully understand the roles of sulfhydration in various biological systems and its potential as a therapeutic target for treating diseases.'
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Proteins (1)

Compounds (15)