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Trypanothione-disulfide reductase

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trypanothione-disulfide reductase
Identifiers
EC no.1.8.1.12
CAS no.102210-35-5
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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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

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  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.