Part:BBa_K2571001
Bifunctional gamma-glutamate-cysteine ligase/Glutathione synthetase
Bifunctional gamma-glutamate-cysteine ligase/glutathione synthetase/GSH
Usage and Biology
Glutathione (GSH) is an important antioxidant that is a sulfur compound; a tripeptide composed of three amino acids (cysteine, glycine and glutamic acid) and a non-protein thiol (Pizzorno, 2014; Lu, 2013). Similar to cysteine, glutathione contains the crucial thiol (-SH) group which benefits to its efficiency as an antioxidant (“Glutathione”, 2005). As a substrate for glutathione S-transferase, which reacts with a number of harmful chemical species, such as halides, epoxides, and free radicals to form harmless products (“Glutathione”, 2005). GSH is generally found in the thiol-reduced from which is crucial for detoxification of ROS and free radicals which cause oxidative stress. (Lu, 2013; Burton & Jauniaux, 2011).
Figure1 : The predicted three-dimensional structure of Bifunctional gamma-glutamate-cysteine ligase from Streptococcus Thermophilus. Data were analysed and modeled by the SWISS-MODEL software. While constructing, the codon bias rule is obeyed to express the enzyme in Escherichia Coli KO11.
During bioethanol production, furfural, HMF and reactive oxygen species (ROS) occur which are converted to less toxic alcohols by oxidoreductases (Ask et al, 2013). Reactive Oxygen Species are dangerous substances that distort protein based matters by taking electrons (Lu, 2013). The chemical structure of the protein-based substances are altered and become dysfunctional because of ROS (Lu, 2013; Burton & Jauniaux, 2011). Furthermore, one of the most significant protein-based substance, DNA get attacked by OH radicals (Burton & Jauniaux, 2011). These attacks cause severe damages to the DNA such as cross-linkages, chromatin folding and strand breakages (Burton & Jauniaux, 2011). However, the reduced form GSH can protect the chemical structure of the proteins by giving extra electrons to the ROS and free radicals (Lu, 2013). This is accomplished by GSH peroxidase-catalyzed reactions (Lu, 2013). When GSH give away its electron, it oxidizes to GSSG (disulfide-oxidized Glutathione ). Then, GSSG is reduced to GSH at the expense of NADPH by Glutathione reductase.
However, the detoxification of ROS and conversion of furfural and HMF result in a more oxidized intracellular environment that deteriorates the antioxidant defense system of the cell (Ask et al., 2013).
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000INCOMPATIBLE WITH RFC[1000]Illegal BsaI.rc site found at 2008
References
Patrick, L. (2003). Mercury Toxicity and Antioxidants: Part I: Role of Glutathione and alpha-Lipoic Acid in the Treatment of Mercury Toxicity. Alternative medicine review: a journal of clinical therapeutic.(7). 456-471. https://www.researchgate.net/publication/10980025_Mercury_Toxicity_and_Antioxidants_Part_I_Role_of_Glutathione_and_alpha-Lipoic_Acid_in_the_Treatment_of_Mercury_Toxicity
Ask, M., Mapelli, V., Höck, H., Olsson, L., Bettiga, M. (2013) Engineering glutathione biosynthesis of Saccharomyces cerevisiae increases robustness to inhibitors in pretreated lignocellulosic materials. Microbial Cell Factories. 12:87 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817835/
Lu, S. C. (2013). GLUTATHIONE SYNTHESIS. Biochemica et Biophysica Acta, 1830(5), 3143–3153. http://doi.org/10.1016/j.bbagen.2012.09.008
National Center for Biotechnology Information. PubChem Compound Database; CID=124886, https://pubchem.ncbi.nlm.nih.gov/compound/124886 (accessed July 18, 2018). https://pubchem.ncbi.nlm.nih.gov/compound/124886#section=Top
Pizzorno, J. (2014). Glutathione! Integrative Medicine: A Clinician’s Journal, 13(1), 8–12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/
Burton, G. J., & Jauniaux, E. (2011). Oxidative stress. Best Practice & Research. Clinical Obstetrics & Gynaecology, 25(3), 287–299. http://doi.org/10.1016/j.bpobgyn.2010.10.016
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