Trypanothione-disulfide reductase
Nowadays, Trypanothione-disulfide reductase is in the focus of many people. Its relevance has grown significantly in different aspects, generating debates, research and multiple opinions on the matter. This topic is of great interest to society in general, since it impacts in some way on people's daily lives. In this article, we will explore different perspectives on Trypanothione-disulfide reductase, its evolution over time and its influence in various areas. Likewise, we will analyze how Trypanothione-disulfide reductase has been gaining importance today and what are the implications of its relevance in different areas.
| trypanothione-disulfide reductase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.8.1.12 | ||||||||
| CAS no. | 102210-35-5 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
In enzymology, a trypanothione-disulfide reductase (EC 1.8.1.12) is an enzyme that catalyzes the chemical reaction
- trypanothione + NADP+ trypanothione disulfide + NADPH + H+
Thus, the two substrates of this enzyme are trypanothione and NADP+, whereas its 3 products are trypanothione disulfide, NADPH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is trypanothione:NADP+ oxidoreductase. Other names in common use include trypanothione reductase, and NADPH2:trypanothione oxidoreductase. It employs one cofactor, FAD.
The X-ray crystal structures of trypanothione reductase enzymes from several trypanosomatids species have been solved, including those from Crithidia fasciculata, Leishmania infantum, Trypanosoma brucei and Trypanosoma cruzi. The structures reveal that trypanothione reductase forms homodimers in solution with each of the two individual subunits comprising an FAD-binding domain, an NADPH-binding domain and an interface domain.[1][2] Examples of trypanothione reductase inhibitors include 5-Nitro-Imidazole,[3] Febrifugine,[4] Imipramine [5] and Benzoxaborole.[6]
References
- ^ Bond, Charles S; Zhang, Yihong; Berriman, Matthew; Cunningham, Mark L; Fairlamb, Alan H; Hunter, William N (1999). "Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors". Structure. 7 (1): 81–89. doi:10.1016/s0969-2126(99)80011-2. PMID 10368274.
- ^ Jones, Deuan C.; Ariza, Antonio; Chow, Wing-Huen A.; Oza, Sandra L.; Fairlamb, Alan H. (2010-01-01). "Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi". Molecular and Biochemical Parasitology. 169 (1): 12–19. doi:10.1016/j.molbiopara.2009.09.002. PMC 2789240. PMID 19747949.
- ^ Pandey RK, Sharma D, Bhatt TK, Sundar S, Prajapati VK (2015). "Developing imidazole analogues as potential inhibitor for Leishmania donovani trypanothione reductase: virtual screening, molecular docking, dynamics and ADMET approach". Journal of Biomolecular Structure and Dynamics. 33 (12): 2541–53. doi:10.1080/07391102.2015.1085904. PMID 26305585. S2CID 205576053.
- ^ Pandey RK, Kumbhar BV, Srivastava S, Malik R, Sundar S, Kunwar A, Prajapati VK (2017). "Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation". Journal of Biomolecular Structure and Dynamics. 35 (1): 141–158. doi:10.1080/07391102.2015.1135298. PMID 27043972. S2CID 3121806.
- ^ Pandey RK, Verma P, Sharma D, Bhatt TK, Sundar S, Prajapati VK (2016). "High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania". Biomedicine & Pharmacotherapy. 83: 141–152. doi:10.1016/j.biopha.2016.06.010. PMID 27470561.
- ^ Pandey RK, Kumbhar BV, Sundar S, Kunwar A, Prajapati VK (2017). "Structure-based virtual screening, molecular docking, ADMET and molecular simulations to develop benzoxaborole analogs as potential inhibitor against Leishmania donovani trypanothione reductase". Journal of Receptors and Signal Transduction. 37 (1): 60–70. doi:10.3109/10799893.2016.1171344. PMID 27147242. S2CID 36383056.
- Shames SL, Fairlamb AH, Cerami A, Walsh CT (1986). "Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases". Biochemistry. 25 (12): 3519–26. doi:10.1021/bi00360a007. PMID 3718941.
- Marsh IR, Bradley M (1997). "Substrate specificity of trypanothione reductase". Eur. J. Biochem. 243 (3): 690–4. doi:10.1111/j.1432-1033.1997.00690.x. PMID 9057833.
- Cunningham ML, Fairlamb AH (1995). "Trypanothione reductase from Leishmania donovani. Purification, characterisation and inhibition by trivalent antimonials". Eur. J. Biochem. 230 (2): 460–8. doi:10.1111/j.1432-1033.1995.tb20583.x (inactive 8 January 2025). PMID 7607216.
{{cite journal}}: CS1 maint: DOI inactive as of January 2025 (link) - Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F (2007). "Betraying the Parasites Redox System: Diaryl Sulfide-Based Inhibitors of Trypanothione Reductase: Subversive Substrates and Antitrypanosomal Properties". ChemMedChem. 2 (12): 1708–12. doi:10.1002/cmdc.200700172. PMID 17918760. S2CID 31754415.
