GO:0016667 oxidoreductase activity, acting on a sulfur group of donors: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016667 describes a molecular function: catalysis of a redox reaction in which a sulfur-containing group donates electrons to an acceptor.
• Key enzyme families include sulfiredoxin (SRXN1), sulfide quinone oxidoreductase (SQOR), molybdenum-cofactor enzymes, and plant sulfur-assimilation enzymes.
• Sulfiredoxin reverses cysteine sulfinic acid oxidation in peroxiredoxins, linking sulfur redox to H2O2 signaling and disease.
• SQOR oxidizes hydrogen sulfide, a gasotransmitter, and is activated by H2S itself, integrating sulfur metabolism with mitochondrial respiration.
• Dysregulation of sulfur-group oxidoreductases contributes to colorectal cancer, liver fibrosis, and systemic redox imbalance in non-communicable diseases.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of these enzymes in human cells and organoids.
Description
Oxidoreductase activity, acting on a sulfur group of donors (GO:0016667) is a molecular function that catalyzes an oxidation-reduction reaction in which a sulfur-containing group serves as the electron donor and reduces an acceptor. This activity is central to sulfur metabolism, antioxidant defense, and redox signaling across all domains of life. The term encompasses enzymes that oxidize thiols, sulfides, sulfoxides, and other sulfur-containing substrates, often using cofactors such as FAD, molybdenum cofactor, or heme. Researchers study GO:0016667 because sulfur redox chemistry underlies diverse physiological processes, from bacterial energy metabolism to human cellular stress responses. In humans, enzymes with this activity, such as sulfiredoxin-1 (SRXN1) and sulfide quinone oxidoreductase (SQOR), modulate hydrogen peroxide and hydrogen sulfide signaling, impacting cancer, fibrosis, and inflammation. Understanding the mechanisms, regulation, and disease relevance of GO:0016667 is therefore essential for both basic biology and therapeutic development.
oxidoreductase activity, acting on a sulfur group of donors At A Glance
| GO ID | GO:0016667 |
|---|---|
| GO term | oxidoreductase activity, acting on a sulfur group of donors |
| Ontology | molecular_function |
| Synonym | oxidoreductase activity, acting on sulfur group of donors, other acceptors; oxidoreductase activity, acting on sulphur group of donors |
| Definition | Catalysis of an oxidation-reduction (redox) reaction in which a sulfur-containing group acts as a hydrogen or electron donor and reduces a hydrogen or electron acceptor. |
| Major function | Electron transfer from sulfur-containing donors to acceptors, often in sulfur metabolism and redox homeostasis. |
| Cofactors | FAD, molybdenum cofactor, heme, and iron-sulfur clusters are commonly used. |
| Representative enzymes | Sulfiredoxin (SRXN1), sulfide quinone oxidoreductase (SQOR), and plant sulfur-assimilation enzymes. |
| Disease links | Colorectal cancer, liver fibrosis, and systemic redox imbalance in non-communicable diseases. |
What Is GO:0016667?
GO:0016667 is defined as the catalysis of an oxidation-reduction (redox) reaction in which a sulfur-containing group acts as a hydrogen or electron donor and reduces a hydrogen or electron acceptor. In simpler terms, it is an enzyme activity that takes electrons from a sulfur-containing molecule and gives them to another molecule, thereby oxidizing the sulfur group. This function is classified under molecular_function in the Gene Ontology and includes enzymes acting on various sulfur donors such as thiols, sulfides, and sulfoxides.
Why Is oxidoreductase activity, acting on a sulfur group of donors Important in Cell Biology?
GO:0016667 is important because sulfur-group oxidation-reduction reactions are fundamental to cellular redox balance, energy metabolism, and signaling. Enzymes with this activity control the fate of reactive sulfur species, including hydrogen sulfide and cysteine sulfinic acid, which influence mitochondrial function, inflammation, and cell survival. Dysregulation of these enzymes is implicated in cancer, fibrosis, and metabolic disorders, making them potential therapeutic targets. Moreover, bacterial sulfur oxidoreductases are key to biogeochemical sulfur cycling and bioleaching, with industrial and environmental applications.
• Maintains redox homeostasis by detoxifying reactive sulfur and oxygen species.
• Regulates hydrogen sulfide signaling, a gasotransmitter involved in vasodilation and neurotransmission.
• Reverses oxidative inactivation of peroxiredoxins via sulfiredoxin, impacting H2O2 signaling.
• Supports plant sulfur assimilation and amino acid biosynthesis.
• Enables bacterial energy generation from sulfur compounds, relevant to bioleaching.
• Contributes to molybdenum cofactor-dependent metabolism in humans and microbes.
• Its dysregulation is linked to colorectal cancer progression and liver fibrosis.
• Altered NRF2 signaling, which interacts with sulfur redox enzymes, is observed in non-communicable diseases.
• Provides targets for CRISPR-based functional genomics and drug discovery.
What Happens During oxidoreductase activity, acting on a sulfur group of donors?
Substrate recognition and binding
In simple terms: The enzyme grabs a sulfur-containing molecule and holds it in place.
Enzymes with GO:0016667 activity bind specific sulfur-containing substrates, such as cysteine sulfinic acid in peroxiredoxins or sulfide ions, through conserved active-site residues. For example, sulfiredoxin-1 (SRXN1) recognizes sulfinylated peroxiredoxins, while SQOR binds sulfide. This binding often involves cofactors like FAD or molybdenum cofactor that facilitate electron transfer.
Electron transfer and catalysis
In simple terms: Electrons are pulled off the sulfur atom and passed to another molecule.
The catalytic cycle involves oxidation of the sulfur donor and reduction of an acceptor, such as oxygen, NAD+, or a quinone. In SQOR, sulfide is oxidized to thiosulfate or sulfate via a flavin-dependent mechanism, transferring electrons to the quinone pool. Molybdenum-cofactor enzymes typically use the metal center to shuttle electrons from sulfur substrates to acceptors.
Product release and enzyme regeneration
In simple terms: The modified sulfur product is released, and the enzyme resets for another round.
After catalysis, the oxidized sulfur product is released, and the enzyme returns to its resting state, often through re-reduction by cellular reductants like glutathione or thioredoxin. Sulfiredoxin-1 requires ATP and a reductant to regenerate its active site after reducing sulfinic acid. This regeneration step is critical for sustained activity under oxidative stress.
Integration with cellular redox networks
In simple terms: These enzymes work as part of a team that keeps the cell's redox balance in check.
GO:0016667 activities are embedded in larger redox networks, including the NRF2 pathway, which regulates antioxidant gene expression. Sulfiredoxin-1 modulates the PTPN12-NLRP3 axis in hepatic stellate cells, linking sulfur redox to inflammation and fibrosis. In plants, sulfur-assimilation enzymes coordinate with nitrogen and carbon metabolism.
Key Genes Involved in GO:0016667 oxidoreductase activity, acting on a sulfur group of donors
The following genes encode enzymes with oxidoreductase activity acting on sulfur group donors, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SRXN1 | Sulfiredoxin-1; reduces cysteine sulfinic acid in peroxiredoxins | Implicated in colorectal cancer and liver fibrosis |
| SQOR | Sulfide quinone oxidoreductase; oxidizes hydrogen sulfide | Regulates H2S signaling and mitochondrial function |
| MOCS1 | Molybdenum cofactor synthesis; supports Mo-dependent sulfur oxidoreductases | Molybdenum cofactor enzymes act on sulfur donors |
| MOCS2 | Molybdenum cofactor synthesis | Required for Mo-enzyme activity |
| GCLM | Glutamate-cysteine ligase modifier; glutathione synthesis | Supports redox homeostasis linked to sulfur metabolism |
| GCLC | Glutamate-cysteine ligase catalytic; glutathione synthesis | Provides reductant for sulfur redox enzymes |
| TXN | Thioredoxin; reduces disulfides | Regenerates sulfiredoxin and other sulfur oxidoreductases |
| TXN2 | Mitochondrial thioredoxin | Supports mitochondrial sulfur redox |
| PRDX1 | Peroxiredoxin 1; substrate of sulfiredoxin | Its sulfinylation is reversed by SRXN1 |
| PRDX2 | Peroxiredoxin 2; substrate of sulfiredoxin | Redox signaling and antioxidant defense |
| PRDX3 | Peroxiredoxin 3; mitochondrial | Mitochondrial H2O2 signaling |
| PRDX4 | Peroxiredoxin 4; ER | ER redox homeostasis |
| NFE2L2 | NRF2; transcription factor regulating antioxidant genes | Altered NRF2 signaling in systemic redox imbalance |
| KEAP1 | CRL3 substrate adaptor; degrades SRXN1 | Regulates SRXN1 stability in cancer |
| PTPN12 | Protein tyrosine phosphatase; modulated by SRXN1 | Involved in liver fibrosis via NLRP3 |
| NLRP3 | Inflammasome sensor; affected by sulfur redox | Inflammation and fibrosis |
| SUOX | Sulfite oxidase; Mo-dependent sulfur oxidation | Molybdenum cofactor enzyme |
| ETHE1 | Persulfide dioxygenase; sulfur oxidation | Mitochondrial sulfur metabolism |
How Is oxidoreductase activity, acting on a sulfur group of donors Regulated?
The activity of enzymes with GO:0016667 is regulated at multiple levels. SRXN1 is targeted for ubiquitin-mediated degradation by the CRL3(Keap1) E3 ligase, linking its stability to the NRF2 antioxidant pathway. SQOR is activated by hydrogen sulfide itself, providing a feed-forward mechanism. In plants, sulfur-assimilation enzymes are transcriptionally regulated in response to sulfur availability. Additionally, NRF2 signaling, which is altered in non-communicable diseases, controls the expression of several antioxidant and sulfur-redox genes.
oxidoreductase activity, acting on a sulfur group of donors and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SRXN1 | Colorectal cancer | Knockout and overexpression in HCT116 or SW480 cells |
| SRXN1 | Liver fibrosis | Knockout in hepatic stellate cells or LX-2 |
| SQOR | Hydrogen sulfide signaling in mitochondrial function | Knockout in HEK293 or HepG2 cells |
| NFE2L2 | Systemic redox imbalance | Knockout or overexpression in patient-derived fibroblasts |
| SUOX | Molybdenum cofactor deficiency | Knockout in HEK293 or patient iPSCs |
Colorectal cancer
SRXN1, a sulfiredoxin with GO:0016667 activity, is degraded by CRL3(Keap1) E3 ligase, and its loss promotes colorectal cancer progression. This suggests that SRXN1 acts as a tumor suppressor in this context, and its regulation by Keap1 is critical.
Liver fibrosis
Sulfiredoxin-1 attenuates hepatic stellate cell activation and liver fibrosis by modulating the PTPN12-NLRP3 axis. This links sulfur-group oxidoreductase activity to inflammatory and fibrotic pathways in the liver.
Systemic redox imbalance in non-communicable diseases
Altered NRF2 signaling, which interacts with sulfur redox enzymes, is observed in non-communicable diseases such as cardiovascular disease and diabetes. This highlights the role of GO:0016667 enzymes in maintaining redox balance and preventing disease.
From oxidoreductase activity, acting on a sulfur group of donors-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does SRXN1 loss promote tumor growth? | SRXN1 knockout in colorectal cancer cell lines |
| How does SQOR activation affect H2S levels? | SQOR knockout and point-mutation in HEK293 cells |
| Can sulfiredoxin-1 reduce liver fibrosis? | SRXN1 overexpression in hepatic stellate cells |
| What is the role of NRF2 in redox imbalance? | NFE2L2 knockout in patient-derived cells |
| How do molybdenum cofactor enzymes function? | MOCS1/MOCS2 knockout in HEK293 |
| Does SRXN1 degradation require Keap1? | Keap1 knockout and SRXN1 tagged knock-in |
How to Study the oxidoreductase activity, acting on a sulfur group of donors Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Gene essentiality and fitness | Identify GO:0016667 genes required for cancer growth |
| Redox proteomics | Cysteine oxidation states | Detect sulfiredoxin substrates |
| H2S quantification | Hydrogen sulfide levels | Assess SQOR activity |
| RNA-seq | Transcriptional changes | Analyze NRF2 target genes |
| Western blot | Protein expression and degradation | Monitor SRXN1 stability |
| Immunoprecipitation | Protein-protein interactions | Study Keap1-SRXN1 binding |
| Metabolic flux analysis | Sulfur metabolite fluxes | Measure sulfur assimilation in plants |
| Bioinformatics pathway enrichment | Functional annotation | Interpret CRISPR screen hits |
CRISPR knockout screens
Genome-wide CRISPR knockout screens can identify genes with GO:0016667 activity that are essential for cancer cell growth or survival. For example, targeting SRXN1 in colorectal cancer cells revealed its tumor-suppressive role.
Proteomics and redox proteomics
Mass spectrometry-based proteomics can quantify oxidation states of sulfur-containing proteins and identify substrates of GO:0016667 enzymes. Redox proteomics specifically detects cysteine sulfinylation and other modifications.
Metabolic assays
Measuring hydrogen sulfide, thiosulfate, and glutathione levels using colorimetric or fluorometric assays assesses the activity of SQOR and related enzymes.
Transcriptomics and bioinformatics
RNA-seq and pathway enrichment analysis can reveal changes in sulfur metabolism and NRF2 target genes upon perturbation of GO:0016667 enzymes.
How CRISPR Can Be Used to Study GO:0016667 oxidoreductase activity, acting on a sulfur group of donors
Knockout
CRISPR knockout of SRXN1 in colorectal cancer cells demonstrated that its loss accelerates tumor progression, establishing it as a tumor suppressor. Similarly, SQOR knockout can be used to study hydrogen sulfide accumulation.
Point Mutation
Introducing point mutations in the catalytic cysteine of SRXN1 or the active-site residues of SQOR can dissect their enzymatic mechanism and substrate specificity.
Knock-in
Tagged knock-in of SRXN1 with a degron or fluorescent tag allows real-time monitoring of its degradation by Keap1 and its subcellular localization.
Overexpression
Overexpression of sulfiredoxin-1 in hepatic stellate cells attenuated activation and fibrosis, suggesting a protective role. Overexpression of SQOR can enhance H2S oxidation.
How EDITGENE Supports oxidoreductase activity, acting on a sulfur group of donors Research
Researchers studying oxidoreductase activity, acting on a sulfur group of donors-related genes often need to determine whether a candidate gene is causally involved in a specific phenotype, such as cancer progression or fibrosis. EDITGENE provides a comprehensive suite of CRISPR services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for oxidoreductase activity, acting on a sulfur group of donors research.
Frequently Asked Questions About oxidoreductase activity, acting on a sulfur group of donors
What is GO:0016667?
GO:0016667 is a Gene Ontology molecular function term for oxidoreductase activity, acting on a sulfur group of donors, which catalyzes redox reactions where a sulfur-containing group donates electrons.
What genes are involved in oxidoreductase activity, acting on a sulfur group of donors?
Key genes include SRXN1, SQOR, MOCS1, MOCS2, SUOX, and ETHE1, among others.
What diseases are linked to sulfur-group oxidoreductases?
They are linked to colorectal cancer, liver fibrosis, and systemic redox imbalance in non-communicable diseases.
How is sulfiredoxin-1 regulated?
SRXN1 is regulated by ubiquitin-mediated degradation via the CRL3(Keap1) E3 ligase.
What is the role of sulfide quinone oxidoreductase?
SQOR oxidizes hydrogen sulfide and is activated by H2S, integrating sulfur metabolism with mitochondrial respiration.
Can CRISPR be used to study GO:0016667 enzymes?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are powerful tools to study these enzymes.
What are the cofactors used by sulfur-group oxidoreductases?
Common cofactors include FAD, molybdenum cofactor, heme, and iron-sulfur clusters.
How does sulfur metabolism relate to NRF2 signaling?
NRF2 regulates antioxidant genes, and altered NRF2 signaling is observed in systemic redox imbalance, interacting with sulfur redox enzymes.
What model systems are used to study plant sulfur oxidoreductases?
Plant models such as Arabidopsis are used to study sulfur assimilation enzymes.
What is the clinical relevance of SRXN1 in liver fibrosis?
Sulfiredoxin-1 attenuates hepatic stellate cell activation and liver fibrosis by modulating the PTPN12-NLRP3 axis.
Conclusion
GO:0016667, oxidoreductase activity acting on a sulfur group of donors, is a fundamental molecular function with broad implications in redox biology, metabolism, and disease. Key enzymes such as SRXN1 and SQOR play critical roles in cancer, fibrosis, and inflammatory pathways. Understanding their mechanisms and regulation through CRISPR-based models will continue to reveal therapeutic opportunities. EDITGENE offers comprehensive services to support such research.
References
- 1. Zhu F et al.. 2024. CRL3(Keap1) E3 ligase facilitates ubiquitin-mediated degradation of oncogenic SRX to suppress colorectal cancer progression.. Nat Commun 15(1):10536 PMID: 39627198
- 2. Roman JV et al.. 2025. Hydrogen sulfide-dependent activation of human sulfide quinone oxidoreductase.. J Biol Chem 301(10):110681 PMID: 40912653
- 3. Cooper AJ. 1983. Biochemistry of sulfur-containing amino acids.. Annu Rev Biochem 52:187-222 PMID: 6351723
- 4. Kim JW et al.. 2025. The desulfinylation enzyme sulfiredoxin-1 attenuates HSC activation and liver fibrosis by modulating the PTPN12-NLRP3 axis.. Hepatology 82(1):92-109 PMID: 39446334
- 5. Xu Z et al.. 2024. Catalysts for sulfur: understanding the intricacies of enzymes orchestrating plant sulfur anabolism.. Planta 261(1):16 PMID: 39690279
- 6. Zhan Y et al.. 2019. Iron and sulfur oxidation pathways of Acidithiobacillus ferrooxidans.. World J Microbiol Biotechnol 35(4):60 PMID: 30919119
- 7. Kisker C et al.. 1997. Molybdenum-cofactor-containing enzymes: structure and mechanism.. Annu Rev Biochem 66:233-67 PMID: 9242907
- 8. Jakubowska M et al.. 2025. Altered NRF2 signalling in systemic redox imbalance: Insights from non-communicable diseases.. Redox Biol 87:103891 PMID: 41109135
