Trypanothione-disulfide reductase
| 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 | ||||||||
| |||||||||
Trypanothione-disulfide reductase (EC 1.8.1.12) is an enzyme that catalyzes the chemical reaction
The three substrates of this enzyme are trypanothione disulfide, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and a proton. Its products are trypanothione and oxidised NADP+.[1][2][3][4][5]
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.[6] The structures reveal that trypanothione reductase forms homodimers in solution with each of the two individual subunits comprising an flavin adenine dinucleotide-binding domain, an NADPH-binding domain and an interface domain.[7] Examples of trypanothione reductase inhibitors include 5-nitroimidazole,[8] febrifugine,[9] imipramine[10] and benzoxaborole.[11]
References
- ^ Enzyme 1.8.1.12 at KEGG Pathway Database.
- ^ 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. PMID 7607216.
- ^ 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.
- ^ 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.