Trypanothione reductase

Function

Trypanothione reductase (TTR) is a flavoenzyme which catalyzes the reaction converting trypanothione (TPT) and NADP to trypanothione disulfide and NADPH. TTR uses FAD as cofactor^[1].

Relevance

TTR is found only in parasitic protozoa, hence its inhibitors are used as effective drugs against diseases like Chagas Disease caused by the parasites Trypanosoma and Leishmania^[2].

Structural highlights

The contains residues which are part of the electron transfer function of the enzyme and the bound TPT substrate^[3].

Trypanosoma FAD-containing trypanothione reductase dimer complex with trypanothione and NADPH 4adw

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3D structures of trypanothione reductase3D structures of trypanothione reductase

Updated on 24-January-2024

ReferencesReferences

↑ Walsh C, Bradley M, Nadeau K. Molecular studies on trypanothione reductase, a target for antiparasitic drugs. Trends Biochem Sci. 1991 Aug;16(8):305-9. PMID:1957352
↑ Rivarola HW, Paglini-Oliva PA. Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas' disease evolution. Curr Drug Targets Cardiovasc Haematol Disord. 2002 Jun;2(1):43-52. PMID:12769656
↑ Baiocco P, Poce G, Alfonso S, Cocozza M, Porretta GC, Colotti G, Biava M, Moraca F, Botta M, Yardley V, Fiorillo A, Lantella A, Malatesta F, Ilari A. Inhibition of Leishmania infantum Trypanothione Reductase by Azole-Based Compounds: a Comparative Analysis with Its Physiological Substrate by X-ray Crystallography. ChemMedChem. 2013 Jun 3. doi: 10.1002/cmdc.201300176. PMID:23733388 doi:10.1002/cmdc.201300176

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Walsh C, Bradley M, Nadeau K. Molecular studies on trypanothione reductase, a target for antiparasitic drugs. Trends Biochem Sci. 1991 Aug;16(8):305-9. PMID:1957352

[2] Rivarola HW, Paglini-Oliva PA. Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas' disease evolution. Curr Drug Targets Cardiovasc Haematol Disord. 2002 Jun;2(1):43-52. PMID:12769656

[3] Baiocco P, Poce G, Alfonso S, Cocozza M, Porretta GC, Colotti G, Biava M, Moraca F, Botta M, Yardley V, Fiorillo A, Lantella A, Malatesta F, Ilari A. Inhibition of Leishmania infantum Trypanothione Reductase by Azole-Based Compounds: a Comparative Analysis with Its Physiological Substrate by X-ray Crystallography. ChemMedChem. 2013 Jun 3. doi: 10.1002/cmdc.201300176. PMID:23733388 doi:10.1002/cmdc.201300176

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