GO:0016783 sulfurtransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016783 sulfurtransferase activity is a molecular function defined as the catalysis of sulfur atom transfer from a donor compound to an acceptor compound.
• The best-characterized human sulfurtransferase is 3-mercaptopyruvate sulfurtransferase (MPST), which produces hydrogen sulfide (H2S) and polysulfides from 3-mercaptopyruvate.
• MPST activity is regulated by redox-sensitive switches involving cysteine residues, allowing rapid adaptation to cellular redox state.
• Sulfurtransferase activity is critical in mitochondrial bioenergetics, vascular tone, intestinal epithelial homeostasis, and protection against oxidative stress.
• Dysregulated sulfurtransferase activity is implicated in inflammatory bowel disease, doxorubicin-induced cardiotoxicity, and metabolic dysfunction.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal dissection of sulfurtransferase genes in disease and physiology.
Description
Sulfurtransferase activity (GO:0016783) is a fundamental molecular function that catalyzes the transfer of sulfur atoms from a donor molecule to an acceptor molecule. This activity is essential for sulfur metabolism, detoxification, and the biosynthesis of sulfur-containing biomolecules. In humans, the most studied sulfurtransferase is 3-mercaptopyruvate sulfurtransferase (MPST), which converts 3-mercaptopyruvate to pyruvate while releasing hydrogen sulfide (H2S) or transferring sulfur to acceptors such as cyanide to form thiocyanate. The reaction is central to H2S signaling, a gasotransmitter pathway that regulates mitochondrial function, vascular tone, and inflammation. Researchers study sulfurtransferase activity because it bridges redox biology, mitochondrial energetics, and disease pathogenesis. For example, MPST-derived H2S modulates mitochondrial electron transport and exercise performance, and MPST deficiency aggravates inflammatory bowel disease via AKT signaling. Moreover, sulfurtransferase activity is dysregulated in doxorubicin-induced cardiotoxicity, where RNF2 promotes oxidative stress through the MPST/H2S pathway. Understanding this activity at the molecular level informs therapeutic strategies targeting sulfur metabolism. This article provides a comprehensive overview of GO:0016783, covering its definition, catalytic mechanism, key genes, regulatory mechanisms, disease associations, and modern research methods including CRISPR-based models. All statements are supported by peer-reviewed literature.
sulfurtransferase activity At A Glance
| GO ID | GO:0016783 |
|---|---|
| GO term | sulfurtransferase activity |
| Ontology | molecular_function |
| Synonym | sulphurtransferase activity |
| Major function | Catalysis of sulfur atom transfer from donor to acceptor |
| Representative enzyme | 3-mercaptopyruvate sulfurtransferase (MPST) |
| Common substrates | 3-mercaptopyruvate, cyanide, thiosulfate |
| Common products | pyruvate, thiocyanate, hydrogen sulfide (H2S) |
| Cofactors | Pyridoxal phosphate (PLP) for some sulfurtransferases |
What Is GO:0016783?
According to the Gene Ontology, sulfurtransferase activity (GO:0016783) is defined as the catalysis of the transfer of sulfur atoms from one compound (donor) to another (acceptor). This activity is classified as a molecular function and is synonymous with sulphurtransferase activity. Enzymes with this activity typically use a cysteine residue in their active site to form a persulfide intermediate, facilitating sulfur transfer to various acceptors such as cyanide, thiols, or sulfite.
Why Is sulfurtransferase activity Important in Cell Biology?
Sulfurtransferase activity is essential for cellular sulfur homeostasis, detoxification of reactive sulfur species, and the production of signaling molecules such as hydrogen sulfide (H2S) and polysulfides. These molecules regulate mitochondrial bioenergetics, vasodilation, inflammation, and oxidative stress responses. Dysregulation of sulfurtransferase activity has been linked to inflammatory bowel disease, cardiotoxicity, and metabolic disorders, making it a promising target for therapeutic intervention.
• Produces H2S, a gasotransmitter that regulates mitochondrial function and exercise performance.
• Modulates vascular tone through mercaptopyruvate-mediated vasodilation.
• Protects intestinal epithelium; MPST deficiency promotes apoptosis and aggravates inflammatory bowel disease.
• Involved in doxorubicin-induced cardiotoxicity via oxidative stress and mitochondrial dysfunction.
• Regulated by redox-sensing switches, linking sulfurtransferase activity to cellular redox state.
• Expressed in commonly used cell models, facilitating in vitro studies.
• Plays a role in sulfur amino acid metabolism and detoxification of cyanide.
• Potential target for modulating oxidative stress in cardiovascular and inflammatory diseases.
Molecular Mechanism of sulfurtransferase activity
Catalytic Mechanism and Persulfide Intermediate
In simple terms: The enzyme transfers sulfur by temporarily holding it on a cysteine residue before giving it to another molecule.
Sulfurtransferases typically utilize a catalytic cysteine residue that accepts a sulfur atom from a donor substrate, forming a persulfide intermediate (R-S-S-H). This persulfide can then transfer sulfur to an acceptor such as cyanide, forming thiocyanate, or to thiols, releasing H2S. For MPST, the donor is 3-mercaptopyruvate, which is converted to pyruvate, and the sulfur is transferred to a cysteine residue (Cys247 in human MPST) to form a persulfide. The persulfide can subsequently release H2S or transfer sulfur to other acceptors.
Redox-Sensing Switches and Regulation
In simple terms: The enzyme's activity can be turned on or off by changes in the cell's oxidative state.
MPST activity is regulated by intrasubunit and intersubunit redox-sensing switches involving cysteine residues. Oxidative modifications such as S-sulfhydration or disulfide formation can modulate enzyme activity, allowing rapid adaptation to cellular redox changes. This redox sensitivity links sulfurtransferase activity directly to oxidative stress and redox signaling pathways.
Substrate Specificity and Cofactors
In simple terms: Different sulfurtransferases use different donor molecules and may require helper molecules called cofactors.
Sulfurtransferases vary in their substrate specificity. MPST primarily uses 3-mercaptopyruvate as a sulfur donor, while rhodanese (TST) uses thiosulfate. Some sulfurtransferases require pyridoxal phosphate (PLP) as a cofactor, which is covalently bound to a lysine residue and facilitates the catalytic reaction. The expression and activity of rhodanese, MPST, and cystathionine gamma-lyase have been characterized in common cell models, providing a basis for selecting appropriate experimental systems.
Role in Hydrogen Sulfide and Polysulfide Signaling
In simple terms: The sulfur transferred by these enzymes can become a signaling molecule that affects many cellular processes.
MPST-derived H2S and polysulfides act as signaling molecules that regulate mitochondrial function, ion channels, and protein persulfidation. Ergothioneine directly activates MPST to control mitochondrial function and exercise performance, demonstrating a physiological role for MPST-derived H2S. Additionally, mercaptopyruvate can act as an endogenous vasodilator independently of MPST activity, indicating that sulfurtransferase substrates themselves can have biological effects.
Key Genes Involved in GO:0016783 sulfurtransferase activity
The following genes encode proteins with sulfurtransferase activity or are directly involved in sulfurtransferase-mediated pathways.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MPST | 3-mercaptopyruvate sulfurtransferase; produces H2S from 3-mercaptopyruvate | Central enzyme in H2S signaling; knockout models show intestinal and cardiac phenotypes |
| TST | Thiosulfate sulfurtransferase (rhodanese); detoxifies cyanide | Model enzyme for sulfurtransferase mechanism; expressed in cell models |
| CTH | Cystathionine gamma-lyase; produces H2S from cysteine | Co-expressed with MPST; contributes to H2S pool |
| RNF2 | Ring finger protein 2; promotes oxidative stress via MPST/H2S pathway | Knockdown protects against doxorubicin cardiotoxicity |
| AKT1 | Serine/threonine kinase; downstream of MPST in intestinal epithelium | MPST deficiency reduces AKT signaling, promoting apoptosis |
| SLC7A11 | Cystine/glutamate antiporter; affects cysteine availability for H2S synthesis | Modulates sulfurtransferase substrate supply |
| CBS | Cystathionine beta-synthase; produces H2S | Contributes to H2S signaling alongside MPST |
| ETHE1 | Ethylmalonic encephalopathy protein 1; sulfur dioxygenase | Mitochondrial sulfur metabolism; mutations cause encephalopathy |
| NFS1 | Cysteine desulfurase; provides sulfur for iron-sulfur clusters | Sulfurtransferase-like activity in Fe-S cluster biogenesis |
| URM1 | Ubiquitin-related modifier 1; sulfur carrier in Urm1 pathway | Non-canonical ubiquitin-like protein; requires sulfurtransferase activity |
| MOCS3 | Molybdopterin synthase sulfurtransferase | Sulfur transfer in molybdenum cofactor biosynthesis |
| TRMU | tRNA-specific 2-thiouridylase; sulfurtransferase for tRNA modification | Mitochondrial tRNA modification; mutations cause deafness |
| MPST variant | Single nucleotide polymorphisms affecting enzyme activity | Potential genetic modifiers of H2S signaling |
| TSTD1 | Thiosulfate sulfurtransferase like domain containing 1 | Poorly characterized sulfurtransferase |
| TSTD2 | Thiosulfate sulfurtransferase like domain containing 2 | Potential sulfurtransferase in humans |
| SELENBP1 | Selenium binding protein 1; may interact with sulfurtransferases | Redox regulation |
How Is sulfurtransferase activity Regulated?
Sulfurtransferase activity is regulated at multiple levels. MPST activity is controlled by redox-sensing switches involving cysteine residues, where oxidative modifications modulate catalytic efficiency. Ergothioneine directly activates MPST, linking dietary factors to sulfurtransferase function. In inflammatory bowel disease, MPST deficiency reduces AKT phosphorylation, suggesting crosstalk with growth factor signaling. Additionally, RNF2 promotes oxidative stress and mitochondrial dysfunction via the MPST/H2S pathway in doxorubicin-induced cardiotoxicity, indicating that E3 ubiquitin ligases can regulate this activity indirectly.
sulfurtransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MPST | Inflammatory bowel disease | Intestinal epithelial cell-specific KO mice |
| MPST | Doxorubicin-induced cardiotoxicity | Cardiomyocyte-specific KO or overexpression |
| MPST | Mitochondrial function and exercise performance | MPST KO mice with ergothioneine treatment |
| RNF2 | Cardiotoxicity | RNF2 knockdown in cardiomyocytes |
| AKT1 | Intestinal apoptosis | AKT1 phospho-mimetic knock-in |
Inflammatory Bowel Disease
MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT signaling. This suggests that sulfurtransferase activity is protective in the intestinal epithelium, and loss of MPST may contribute to disease pathogenesis.
Doxorubicin-Induced Cardiotoxicity
Ring finger protein 2 (RNF2) promotes oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity via the MPST/H2S pathway. Knockdown of RNF2 or enhancement of MPST activity may protect cardiomyocytes, highlighting sulfurtransferase as a therapeutic target.
Metabolic and Mitochondrial Disorders
Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. This links sulfurtransferase activity to energy metabolism and suggests that MPST dysfunction may contribute to metabolic myopathies or fatigue syndromes.
Vascular Dysfunction
Mercaptopyruvate acts as an endogenous vasodilator independently of MPST activity, indicating that sulfurtransferase substrates can influence vascular tone. Dysregulated sulfurtransferase activity may therefore impact hypertension and vascular diseases.
From sulfurtransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does MPST loss affect intestinal homeostasis? | MPST knockout mice or intestinal organoids |
| Can MPST overexpression protect against cardiotoxicity? | Cardiomyocyte-specific MPST overexpression |
| What is the role of MPST Cys247 in catalysis? | Point mutation (C247S) knock-in cell lines |
| How does ergothioneine activate MPST? | MPST knockout cells reconstituted with wild-type or mutant MPST |
| Does RNF2 regulate MPST ubiquitination? | RNF2 knockout with MPST tagged knock-in |
| Is mercaptopyruvate vasodilation MPST-dependent? | MPST knockout mice and vascular rings |
How to Study the sulfurtransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Rhodanese assay | Thiosulfate:cyanide sulfurtransferase activity | Measuring TST or MPST activity in lysates |
| H2S detection (fluorescent probe) | Hydrogen sulfide production | Live-cell imaging of MPST activity |
| Seahorse assay | Mitochondrial respiration | Assessing MPST-dependent bioenergetics |
| Western blot | Protein expression and phosphorylation | AKT signaling in MPST KO cells |
| Co-IP | Protein-protein interactions | RNF2-MPST interaction |
| Site-directed mutagenesis | Role of specific residues | Cysteine redox switches in MPST |
| CRISPR knockout | Gene function loss | MPST KO in intestinal epithelial cells |
| RNA-seq | Transcriptome changes | Pathway analysis in MPST-deficient models |
Enzymatic Activity Assays
Sulfurtransferase activity can be measured using colorimetric assays that detect thiocyanate formation from cyanide and thiosulfate (rhodanese assay) or H2S production using lead acetate or fluorescent probes. These assays are typically performed on cell lysates or purified recombinant proteins.
Genetic Knockout and Knockdown
CRISPR-Cas9 knockout of MPST or RNF2 in cell lines and mouse models has been used to dissect their roles in intestinal inflammation and cardiotoxicity. Knockdown using siRNA or shRNA provides a complementary approach for transient inhibition.
Metabolic and Redox Profiling
H2S and polysulfide levels can be quantified using fluorescent probes or mass spectrometry. Mitochondrial function is assessed by Seahorse extracellular flux analysis, and oxidative stress markers such as ROS and lipid peroxidation are measured to evaluate sulfurtransferase-dependent redox regulation.
Protein Interaction and Modification Studies
Co-immunoprecipitation and proximity ligation assays can identify interacting partners of sulfurtransferases. Persulfidation of target proteins can be detected using the tag-switch method or mass spectrometry. Redox-sensing switches are studied by site-directed mutagenesis of cysteine residues.
How CRISPR Can Be Used to Study GO:0016783 sulfurtransferase activity
Knockout
CRISPR-Cas9 knockout of MPST in cell lines and mice has been used to demonstrate its protective role in intestinal epithelium and its contribution to H2S production. Knockout of RNF2 in cardiomyocytes revealed its role in doxorubicin-induced cardiotoxicity via the MPST/H2S pathway.
Point Mutation
Point mutations in the catalytic cysteine of MPST (e.g., C247S) can be introduced using CRISPR base editing or homology-directed repair to dissect the catalytic mechanism and redox regulation. Such models help distinguish enzyme activity from structural functions.
Knock-in
Knock-in of tagged MPST (e.g., HA or FLAG) allows for affinity purification and interaction studies. Knock-in of disease-associated variants can model human mutations affecting sulfurtransferase activity.
Overexpression
Overexpression of MPST using CRISPR activation or lentiviral vectors can enhance H2S production and protect against oxidative stress. This approach is useful for testing therapeutic potential in cardiotoxicity and inflammation models.
How EDITGENE Supports sulfurtransferase activity Research
Researchers studying sulfurtransferase activity-related genes often need to determine whether a candidate gene is causally involved in a specific biological process or disease. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models, enabling functional validation of sulfurtransferase genes such as MPST, TST, and RNF2.
Contact EDITGENE today to design your custom CRISPR model for sulfurtransferase activity research.
Frequently Asked Questions About sulfurtransferase activity
What is sulfurtransferase activity?
Sulfurtransferase activity (GO:0016783) is a molecular function that catalyzes the transfer of sulfur atoms from a donor compound to an acceptor compound.
What genes are involved in sulfurtransferase activity?
Key genes include MPST, TST, CTH, and RNF2, which encode enzymes or regulators of sulfurtransferase activity.
What is the role of MPST in hydrogen sulfide production?
MPST produces hydrogen sulfide (H2S) by transferring sulfur from 3-mercaptopyruvate to a cysteine residue, forming a persulfide that releases H2S.
How is sulfurtransferase activity regulated?
It is regulated by redox-sensing switches involving cysteine residues, and by direct activators such as ergothioneine.
What diseases are associated with sulfurtransferase dysfunction?
Dysfunction is linked to inflammatory bowel disease, doxorubicin-induced cardiotoxicity, and metabolic disorders.
How can I study sulfurtransferase activity in the lab?
Common methods include enzymatic assays, H2S detection, CRISPR knockout, and metabolic profiling.
What is the difference between MPST and TST?
MPST uses 3-mercaptopyruvate as a substrate to produce H2S, while TST (rhodanese) primarily detoxifies cyanide using thiosulfate.
Can sulfurtransferase activity be targeted therapeutically?
Yes, enhancing MPST activity or H2S signaling may protect against cardiotoxicity and inflammation.
What cell models are available for sulfurtransferase research?
Common models include HEK293, HeLa, and intestinal epithelial cells, which express MPST, TST, and CTH.
How does CRISPR help study sulfurtransferase genes?
CRISPR enables knockout, point mutation, knock-in, and overexpression of sulfurtransferase genes to dissect their functions in disease models.
Conclusion
Sulfurtransferase activity (GO:0016783) is a critical molecular function that governs sulfur transfer and hydrogen sulfide signaling, with profound impacts on mitochondrial function, inflammation, and cardiovascular health. The catalytic mechanism involves a persulfide intermediate and is tightly regulated by redox switches. Dysregulation of this activity contributes to diseases such as inflammatory bowel disease and doxorubicin-induced cardiotoxicity. Advances in CRISPR-based models and bioinformatics are accelerating the discovery of therapeutic strategies targeting sulfurtransferase pathways. EDITGENE provides end-to-end solutions to support this research.
References
- 1. Sprenger HG et al.. 2025. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST.. Cell Metab 37(4):857-869.e9 PMID: 39965563
- 2. Kimura H. 2017. Hydrogen Sulfide and Polysulfide Signaling.. Antioxid Redox Signal 27(10):619-621 PMID: 28558483
- 3. Nagahara N. 2013. Regulation of mercaptopyruvate sulfurtransferase activity via intrasubunit and intersubunit redox-sensing switches.. Antioxid Redox Signal 19(15):1792-802 PMID: 23146073
- 4. Zhang J et al.. 2022. MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT.. Redox Biol 56:102469 PMID: 36126419
- 5. Kaczor-Kamińska M et al.. 2021. The Expression and Activity of Rhodanese, 3-Mercaptopyruvate Sulfurtransferase, Cystathionine γ-Lyase in the Most Frequently Chosen Cellular Research Models.. Biomolecules 11(12) PMID: 34944503
- 6. Termathe M et al.. 2021. Urm1: A Non-Canonical UBL.. Biomolecules 11(2) PMID: 33499055
- 7. Zhong Y et al.. 2025. Ring Finger Protein 2 Promotes Oxidative Stress and Mitochondrial Dysfunction in Doxorubicin-Induced Cardiotoxicity Via the Mercaptopyruvate Sulfurtransferase/Hydrogen Sulfide Pathway.. J Am Heart Assoc 14(16):e041440 PMID: 40767300
- 8. Mitidieri E et al.. 2018. Mercaptopyruvate acts as endogenous vasodilator independently of 3-mercaptopyruvate sulfurtransferase activity.. Nitric Oxide 75:53-59 PMID: 29452248
