Biological and Catalytic Properties of Selenoproteins
Abstract
:1. Introduction
2. Co-Translational Incorporation of Selenocysteine
3. Mammalian Selenoproteins
3.1. Selenophosphate Synthetase
3.2. Selenoprotein P (Selenop)
3.3. Selenium-Glutathione Peroxidases (Se-GPx)
3.3.1. GPx1
Type | Localization | Structure | Reducing Cosubstrate | Hydroperoxide Substrates | Inhibitors Inactivators | Function 2 |
---|---|---|---|---|---|---|
GPx1 | Ubiquitous in cytosol and mitochondrial matrix | Homotetramer, five conserved residues at GSH binding site (four Arg, one Lys) | GSH | H2O2 and alkyl hydroperoxides | Mercaptosuccinate 3 O2.−, HOCl Heavy metals | Antioxidant Redox regulator? |
GPx2 | Cytosol of epithelial cells | Homotetramer, extracellular glycoprotein | GSH | H2O2 and alkyl hydroperoxides | undocumented | Antioxidant Redox regulator? |
GPx3 | Mostly extracell. Blood plasma, Secreted/kidney mammary gland | Homotetramer, Glycoprotein | Thioredoxin; GSH (nonphysiological) | H2O2 and alkyl hydroperoxides | undocumented | Antioxidant Redox regulator? |
GPx4 | Membrane-bound Cytoplasm Mitochondria Nucleus (minor) | Monomer | Thioredoxin Protein thiols GSH (nonphysiological), | Phospholipid-OOH, Cholesterol-OOH, LDL-OOH | RSL3 ML162 | Antiox/Redox regul? Anti-ferroptosis Spermatozoid specific- protein crosslinker |
GpX6 | Olfactory epithelium | Homotetramer, Strong sequence homology with GPx3 | Thioredoxin; GSH? | undocumented | undocumented | Antioxidant Redox regulator? |
3.3.2. GPx2
3.3.3. GPx3
3.3.4. GPx4
3.3.5. Other Members of the GPx Family
3.3.6. Mechanistic Complexity of Glutathione Peroxidases
3.4. Thioredoxin Reductases (TrxR)
3.5. Selenium-Dependent Deiodinases
3.6. Methionine R-Sulfoxide Reductase B1 [MsrB1]
3.7. Other Mammalian Selenoproteins
3.7.1. Selenoprotein O and Protein AMPylation
3.7.2. Selenoprotein F and Endoplasmic Reticulum Glycoproteins
3.7.3. Selenoprotein N and Endoplasmic Reticulum Calcium Sensing
3.7.4. Selenoprotein I and Ethanolamine Phospholipids
3.7.5. Selenoprotein K, Palmitoylation Cofactor and Inhibitor of ER-Induced Apoptosis
3.7.6. Selenoprotein W and EGF Regulation
3.7.7. Selenoprotein T
3.7.8. Selenoprotein S
3.7.9. Selenoprotein-H
4. Bacterial Selenoenzymes
4.1. Glycine Reductase
4.2. D-Proline Reductase
4.3. Formate Dehydrogenase
4.4. [NiFeSe] Hydrogenases
5. Is Redox Regulation an Essential Function of Most Mammalian Selenoproteins?
6. Advantages and Constraints Associated with the Choice of Selenocysteine at the Active Site of Selenoenzymes
7. Conclusions
- The co-translational incorporation of selenium in selenoproteins is probably unique among the elements situated below period 3 of the periodic table, and one of the major advantages of selenium compared with sulfur should be the better reversibility of its oxidation reactions in biological conditions.
- Selenoproteins are mostly involved in anaerobic metabolism in bacteria, whereas they are involved in antioxidant protection, protein repair, redox signaling, and regulation of cell proliferation/cell death, and energetic metabolism in mammals.
- Many functions of mammalian selenoproteins, especially those which are anti-inflammatory, anti-apoptotic, or anti-ferroptotic, or which interfere with energetic metabolism, require regulation in space and time. Specifically, most mammalian selenoenzymes should not only be regulating but also regulated, although, in this area, much information is probably still missing.
- With the recent development of new techniques of selenocysteine insertion into protein sequences, we can expect that new discoveries will shed light on the hidden face of the moon.
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AIF, apoptosis inducing factor; Alkbh, mammalian alkylation repair homolog; Alox15 gene, gene encoding an arachidonate 15-lipoxygenase; AP-1, activator protein 1; ASK1, apoptosis signal kinase 1; CAMKII, Ca2+ calmodulin-dependent kinase; COX2, Type 2 cyclooxygenase; DIO, deiodinase; DUOX, dual oxidase; EFsec, selenocysteine dedicated elongation factor; EMT, epithelial-mesenchymal transition; GLS2, liver-type glutaminase; GPx, glutathione peroxidase; GR, glutathione reductase; HCV, hepatitis C virus; HIF, hypoxia inducible factor; Keap1, Kelch associated protein 1; LOX, Lipoxygenase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MICAL, molecules interacting with CasL; MsrB1, methionine sulfoxide reductase B1; NFκB, nuclear factor kB; Nox, NADPH oxidase; Nrf2, nuclear factor erythroid-2-related factor; NQQ1, NAD[P)H: Quinone oxidoreductase 1; PDI, protein disulfide isomerase; Prx, peroxiredoxin; PTEN, phosphatase and tensin homolog; SBP2, SECIS-binding protein 2; SecTRAPs, selenium compromised thioredoxin reductase-derived apoptotic proteins; SECYS, selenocysteine insertion sequence; Selenoprotein P, selenoprotein P; Sephs2, selenophosphate synthetase 2; TGS1, trimethylguanosine synthase 1; TNFα, tumor necrosis factor a; TPO, thyroid peroxidase; Trx, thioredoxin; TrxR, thioredoxin reductase; T4, thyroxine; T3 triiodothyronine; ZEB1, zinc-finger E-box binding protein 1. |
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Chaudière, J. Biological and Catalytic Properties of Selenoproteins. Int. J. Mol. Sci. 2023, 24, 10109. https://doi.org/10.3390/ijms241210109
Chaudière J. Biological and Catalytic Properties of Selenoproteins. International Journal of Molecular Sciences. 2023; 24(12):10109. https://doi.org/10.3390/ijms241210109
Chicago/Turabian StyleChaudière, Jean. 2023. "Biological and Catalytic Properties of Selenoproteins" International Journal of Molecular Sciences 24, no. 12: 10109. https://doi.org/10.3390/ijms241210109