TSTD1 Human
Description
Functional Role in Hydrogen Sulfide Metabolism
TSTD1 catalyzes the transfer of sulfane sulfur from thiosulfate to glutathione, producing S-sulfanylglutathione (GSS⁻), a central intermediate in H₂S metabolism .
Key Reactions:
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Thiosulfate:Glutathione Sulfurtransferase Activity:
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Interaction with Sulfur Dioxygenase (SDO):
GSS⁻ serves as a substrate for SDO, which oxidizes it to sulfite. This coupling ensures efficient H₂S oxidation .
Kinetic Parameters:
| Parameter | TSTD1 (Human) | Yeast RDL1 |
|---|---|---|
| Kₘ (Thiosulfate) | 1.8 mM | 0.6 mM |
| Kₘ (GSH) | 0.5 mM | 0.3 mM |
| kcat | 0.2 s⁻¹ | 5.0 s⁻¹ |
| kcat/Kₘ (GSH) | 0.4 mM⁻¹s⁻¹ | 16.7 mM⁻¹s⁻¹ |
| Data from |
Cancer Biomarker and Therapeutic Target:
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Promoter Hypomethylation: Observed in breast cancer, leading to TSTD1 overexpression (68.8% in Taiwanese/Korean cohorts). Correlates with poor 5-year survival (p = 0.021) and chemotherapy resistance (p = 0.008) .
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Colorectal Cancer: Apical localization in colonic crypts suggests interaction with sulfide-producing microbes. Overexpression linked to tumor progression .
Metabolic Regulation:
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HDL Modulation: TSTD1 influences plasma HDL levels and mitochondrial function, potentially affecting lipid metabolism .
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Chemical Interactions:
Thioredoxin (TRX) Dependency:
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Low Kₘ for TRX: TSTD1 exhibits Kₘ = 0.2 mM for TRX as a sulfane sulfur acceptor, suggesting a role in sulfide-based signaling .
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Antioxidant Crosstalk: Potential regulation of ASK1/p38 MAPK and PTP1B pathways via glutathionylation .
Sulfane Sulfur Transfer Pathways:
| Sulfur Donor | Sulfur Acceptor | Biological Role |
|---|---|---|
| Thiosulfate | Glutathione | H₂S oxidation |
| Thioredoxin | Coenzyme A | Redox signaling |
| p-Tol-SO₂⁻ | N/A | Detoxification (in vitro) |
| Data from |
Expression and Localization
Subcellular Localization:
Research Challenges and Future Directions
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Isoform Complexity: Only isoform 1 (115 aa) is catalytically active; smaller isoforms lack function .
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Therapeutic Potential: Targeting TSTD1 in cancer (e.g., siRNA knockdown reduces proliferation ) or metabolic disorders (e.g., HDL regulation ).
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Mechanistic Gaps: Role in iron-sulfur cluster biogenesis and cyanide detoxification requires further validation .
Product Specs
MGSSHHHHHH SSGLVPRGSH MAGAPTVSLP ELRSLLASGR ARLFDVRSRE EAAAGTIPGA LNIPVSELES ALQMEPAAFQ ALYSAEKPKL EDEHLVFFCQ MGKRGLQATQ LARSLGYTGA RNYAGAYREW LEKES.
Product Science Overview
The TSTD1 gene is located on chromosome 1q23.3 and encodes a protein that is approximately 12.5 kDa in size . The protein contains a rhodanese-like domain, which is essential for its sulfurtransferase activity. This domain includes a catalytic cysteine residue that is crucial for the enzyme’s function .
TSTD1 is involved in the intermediate step of H2S metabolism. It catalyzes the conversion of thiosulfate and glutathione to sulfite and glutathione persulfide . This reaction is essential for the detoxification of H2S and the regulation of its signaling functions. The enzyme works in conjunction with other enzymes such as sulfide:quinone oxidoreductase (SQOR) and sulfur dioxygenase (SDO) to ensure efficient H2S metabolism .
