Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Trypanothione Metabolism as Drug Target for Trypanosomatids

Author(s): María Dolores Piñeyro, Diego Arias, Adriana Parodi-Talice, Sergio Guerrero and Carlos Robello*

Volume 27, Issue 15, 2021

Published on: 11 December, 2020

Page: [1834 - 1846] Pages: 13

DOI: 10.2174/1381612826666201211115329

Price: $65

Abstract

Chagas Disease, African sleeping sickness, and leishmaniasis are neglected diseases caused by pathogenic trypanosomatid parasites, which have a considerable impact on morbidity and mortality in poor countries. The available drugs used as treatment have high toxicity, limited access, and can cause parasite drug resistance. Long-term treatments, added to their high toxicity, result in patients that give up therapy. Trypanosomatids presents a unique trypanothione based redox system, which is responsible for maintaining the redox balance. Therefore, inhibition of these essential and exclusive parasite’s metabolic pathways, absent from the mammalian host, could lead to the development of more efficient and safe drugs. The system contains different redox cascades, where trypanothione and tryparedoxins play together a central role in transferring reduced power to different enzymes, such as 2-Cys peroxiredoxins, non-selenium glutathione peroxidases, ascorbate peroxidases, glutaredoxins and methionine sulfoxide reductases, through NADPH as a source of electrons. There is sufficient evidence that this complex system is essential for parasite survival and infection. In this review, we explore what is known in terms of essentiality, kinetic and structural data, and the development of inhibitors of enzymes from this trypanothione-based redox system. The recent advances and limitations in the development of lead inhibitory compounds targeting these enzymes have been discussed. The combination of molecular biology, bioinformatics, genomics, and structural biology is fundamental since the knowledge of unique features of the trypanothione-dependent system will provide tools for rational drug design in order to develop better treatments for these diseases.

Keywords: Trypanothione, Kinetoplastid, redox metabolism, inhibitor, drug target, Trypanosoma, Leishmania.

« Previous Next »
[1]
Wilson AL, Courtenay O, Kelly-Hope LA, et al. The importance of vector control for the control and elimination of vector-borne diseases. PLoS Negl Trop Dis 2020; 14(1): e0007831.
[http://dx.doi.org/10.1371/journal.pntd.0007831] [PMID: 31945061]
[2]
Kennedy PGE. Update on human African trypanosomiasis (sleeping sickness). J Neurol 2019; 266(9): 2334-7.
[http://dx.doi.org/10.1007/s00415-019-09425-7] [PMID: 31209574]
[3]
Franco JR, Cecchi G, Priotto G, et al. Monitoring the elimination of human African trypanosomiasis at continental and country level: Update to 2018. PLoS Negl Trop Dis 2020; 14(5): e0008261.
[http://dx.doi.org/10.1371/journal.pntd.0008261] [PMID: 32437391]
[4]
Pérez-Molina JA, Molina I. Chagas disease cardiomyopathy treatment remains a challenge - Authors’ reply. Lancet 2018; 391(10136): 2209-10.
[http://dx.doi.org/10.1016/S0140-6736(18)30776-1] [PMID: 29893217]
[5]
Manne-Goehler J, Umeh CA, Montgomery SP, Wirtz VJ. Estimating the burden of Chagas disease in the United States. PLoS Negl Trop Dis 2016; 10(11): e0005033.
[http://dx.doi.org/10.1371/journal.pntd.0005033] [PMID: 27820837]
[6]
Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet 2018; 392(10151): 951-70.
[http://dx.doi.org/10.1016/S0140-6736(18)31204-2] [PMID: 30126638]
[7]
Dumonteil E, Herrera C, Buekens P. A therapeutic preconceptional vaccine against Chagas disease: A novel indication that could reduce congenital transmission and accelerate vaccine development. PLoS Negl Trop Dis 2019; 13(1): e0006985.
[http://dx.doi.org/10.1371/journal.pntd.0006985] [PMID: 30703092]
[8]
Hotez PJ, Pecoul B, Rijal S, et al. Eliminating the neglected tropical diseases: translational science and new technologies. PLoS Negl Trop Dis 2016; 10(3): e0003895.
[http://dx.doi.org/10.1371/journal.pntd.0003895] [PMID: 26934395]
[9]
Hotez PJ, Bottazzi ME, Strych U. New vaccines for the World’s poorest people. Annu Rev Med 2016; 67: 405-17.
[http://dx.doi.org/10.1146/annurev-med-051214-024241] [PMID: 26356803]
[10]
Santos SS, de Araújo RV, Giarolla J, Seoud OE, Ferreira EI. Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. Int J Antimicrob Agents 2020; 55(4): 105906.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105906] [PMID: 31987883]
[11]
Engels D, Zhou XN. Neglected tropical diseases: an effective global response to local poverty-related disease priorities. Infect Dis Poverty 2020; 9(1): 10.
[http://dx.doi.org/10.1186/s40249-020-0630-9] [PMID: 31987053]
[12]
Jones NG, Catta-Preta CMC, Lima APCA, Mottram JC. Genetically validated drug targets in Leishmania: current knowledge and future prospects. ACS Infect Dis 2018; 4(4): 467-77.
[http://dx.doi.org/10.1021/acsinfecdis.7b00244] [PMID: 29384366]
[13]
Osorio-Méndez JF, Cevallos AM. Discovery and genetic validation of chemotherapeutic targets for Chagas’ disease. Front Cell Infect Microbiol 2019; 8: 439.
[http://dx.doi.org/10.3389/fcimb.2018.00439] [PMID: 30666299]
[14]
Fairlamb AH, Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol 1992; 46(1): 695-729.
[http://dx.doi.org/10.1146/annurev.mi.46.100192.003403] [PMID: 1444271]
[15]
Krauth-Siegel RL, Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta 2008; 1780(11): 1236-48.
[http://dx.doi.org/10.1016/j.bbagen.2008.03.006] [PMID: 18395526]
[16]
Irigoín F, Cibils L, Comini MA, Wilkinson SR, Flohé L, Radi R. Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification. Free Radic Biol Med 2008; 45(6): 733-42.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.05.028] [PMID: 18588970]
[17]
Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 1985; 227(4693): 1485-7.
[http://dx.doi.org/10.1126/science.3883489] [PMID: 3883489]
[18]
Ariyanayagam MR, Oza SL, Mehlert A, Fairlamb AH. Bis(glutathionyl)spermine and other novel trypanothione analogues in Trypanosoma cruzi. J Biol Chem 2003; 278(30): 27612-9.
[http://dx.doi.org/10.1074/jbc.M302750200] [PMID: 12750367]
[19]
Flohé L, Hecht HJ, Steinert P. Glutathione and trypanothione in parasitic hydroperoxide metabolism. Free Radic Biol Med 1999; 27(9-10): 966-84.
[http://dx.doi.org/10.1016/S0891-5849(99)00172-0] [PMID: 10569629]
[20]
Ariyanayagam MR, Fairlamb AH. Ovothiol and trypanothione as antioxidants in trypanosomatids. Mol Biochem Parasitol 2001; 115(2): 189-98.
[http://dx.doi.org/10.1016/S0166-6851(01)00285-7] [PMID: 11420105]
[21]
Moutiez M, Meziane-Cherif D, Aumercier Sergheraert C, Tartar A. Compared reactivities of trypanothione and glutathione in conjugation reactions 1994; 42(12): 2641-4.
[http://dx.doi.org/10.1248/cpb.42.2641]
[22]
Krauth-Siegel RL, Meiering SK, Schmidt H. The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Biol Chem 2003; 384(4): 539-49.
[http://dx.doi.org/10.1515/BC.2003.062] [PMID: 12751784]
[23]
Meziane-Cherif D, Aumercier M, Sergheraert C, Tartar A. Compared reactivities of trypanothione and glutathione in conjugation reactions. Chem Pharm Bull (Tokyo) 1994; 42(12): 2641-4.
[http://dx.doi.org/10.1248/cpb.42.2641]
[24]
Gommel DU, Nogoceke E, Morr M, Kiess M, Kalisz HM, Flohé L. Catalytic characteristics of tryparedoxin. Eur J Biochem 1997; 248(3): 913-8.
[http://dx.doi.org/10.1111/j.1432-1033.1997.t01-1-00913.x] [PMID: 9342246]
[25]
Guerrero SA, Lopez JA, Steinert P, et al. His-tagged tryparedoxin peroxidase of Trypanosoma cruzi as a tool for drug screening. Appl Microbiol Biotechnol 2000; 53(4): 410-4.
[http://dx.doi.org/10.1007/s002530051634] [PMID: 10803896]
[26]
Hillebrand H, Schmidt A, Krauth-Siegel RL. A second class of peroxidases linked to the trypanothione metabolism. J Biol Chem 2003; 278(9): 6809-15.
[http://dx.doi.org/10.1074/jbc.M210392200] [PMID: 12466271]
[27]
Nogoceke E, Gommel DU, Kiess M, Kalisz HM, Flohé L. A unique cascade of oxidoreductases catalyses trypanothione-mediated peroxide metabolism in Crithidia fasciculata. Biol Chem 1997; 378(8): 827-36.
[http://dx.doi.org/10.1515/bchm.1997.378.8.827] [PMID: 9377478]
[28]
Wilkinson SR, Meyer DJ, Taylor MC, Bromley EV, Miles MA, Kelly JM. The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin. J Biol Chem 2002; 277(19): 17062-71.
[http://dx.doi.org/10.1074/jbc.M111126200] [PMID: 11842085]
[29]
Wilkinson SR, Temperton NJ, Mondragon A, Kelly JM. Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi. J Biol Chem 2000; 275(11): 8220-5.
[http://dx.doi.org/10.1074/jbc.275.11.8220] [PMID: 10713147]
[30]
Oza SL, Tetaud E, Ariyanayagam MR, Warnon SS, Fairlamb AH. A single enzyme catalyses formation of Trypanothione from glutathione and spermidine in Trypanosoma cruzi. J Biol Chem 2002; 277(39): 35853-61.
[http://dx.doi.org/10.1074/jbc.M204403200] [PMID: 12121990]
[31]
Comini M, Menge U, Flohé L. Biosynthesis of trypanothione in Trypanosoma brucei brucei. Biol Chem 2003; 384(4): 653-6.
[http://dx.doi.org/10.1515/BC.2003.072] [PMID: 12751794]
[32]
Oza SL, Shaw MP, Wyllie S, Fairlamb AH. Trypanothione biosynthesis in Leishmania major. Mol Biochem Parasitol 2005; 139(1): 107-16.
[http://dx.doi.org/10.1016/j.molbiopara.2004.10.004] [PMID: 15610825]
[33]
Fyfe PK, Oza SL, Fairlamb AH, Hunter WN. Leishmania trypanothione synthetase-amidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities. J Biol Chem 2008; 283(25): 17672-80.
[http://dx.doi.org/10.1074/jbc.M801850200] [PMID: 18420578]
[34]
Comini M, Menge U, Wissing J, Flohé L. Trypanothione synthesis in crithidia revisited. J Biol Chem 2005; 280(8): 6850-60.
[http://dx.doi.org/10.1074/jbc.M404486200] [PMID: 15537651]
[35]
Sousa AF, Gomes-Alves AG, Benítez D, et al. Genetic and chemical analyses reveal that trypanothione synthetase but not glutathionylspermidine synthetase is essential for Leishmania infantum. Free Radic Biol Med 2014; 73: 229-38.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.05.007] [PMID: 24853758]
[36]
Wyllie S, Oza SL, Patterson S, Spinks D, Thompson S, Fairlamb AH. Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods. Mol Microbiol 2009; 74(3): 529-40.
[http://dx.doi.org/10.1111/j.1365-2958.2009.06761.x] [PMID: 19558432]
[37]
Jiang Y, Roberts SC, Jardim A, et al. Ornithine decarboxylase gene deletion mutants of Leishmania donovani. J Biol Chem 1999; 274(6): 3781-8.
[http://dx.doi.org/10.1074/jbc.274.6.3781] [PMID: 9920931]
[38]
Ariyanayagam MR, Oza SL, Guther ML, Fairlamb AH. Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome. Biochem J 2005; 391(Pt 2): 425-32.
[http://dx.doi.org/10.1042/BJ20050911] [PMID: 16008527]
[39]
Comini MA, Guerrero SA, Haile S, Menge U, Lünsdorf H, Flohé L. Validation of Trypanosoma brucei trypanothione synthetase as drug target. Free Radic Biol Med 2004; 36(10): 1289-302.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.02.008] [PMID: 15110394]
[40]
Mesías AC, Sasoni N, Arias DG, et al. Trypanothione synthetase confers growth, survival advantage and resistance to anti-protozoal drugs in Trypanosoma cruzi. Free Radic Biol Med 2019; 130: 23-34.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.436] [PMID: 30359758]
[41]
Koch O, Jaeger T, Flohé L, Selzer P. Inhibition of Trypanothione Synthetase as a therapeutic concept. Willey-Blackwell 2013.
[42]
Saudagar P, Saha P, Saikia AK, Dubey VK. Molecular mechanism underlying antileishmanial effect of oxabicyclo[3.3.1]nonanones: inhibition of key redox enzymes of the pathogen. Eur J Pharm Biopharm 2013; 85(3 Pt A): 569-77.
[http://dx.doi.org/10.1016/j.ejpb.2013.08.014] [PMID: 24002022]
[43]
Spinks D, Torrie LS, Thompson S, et al. Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors. ChemMedChem 2012; 7(1): 95-106.
[http://dx.doi.org/10.1002/cmdc.201100420] [PMID: 22162199]
[44]
Torrie LS, Wyllie S, Spinks D, et al. Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis. J Biol Chem 2009; 284(52): 36137-45.
[http://dx.doi.org/10.1074/jbc.M109.045336] [PMID: 19828449]
[45]
Benítez D, Medeiros A, Fiestas L, et al. Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids. PLoS Negl Trop Dis 2016; 10(4): e0004617.
[http://dx.doi.org/10.1371/journal.pntd.0004617] [PMID: 27070550]
[46]
Krauth-Siegel RL, Enders B, Henderson GB, Fairlamb AH, Schirmer RH. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur J Biochem 1987; 164(1): 123-8.
[http://dx.doi.org/10.1111/j.1432-1033.1987.tb11002.x] [PMID: 3549299]
[47]
Dumas C, Ouellette M, Tovar J, et al. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J 1997; 16(10): 2590-8.
[http://dx.doi.org/10.1093/emboj/16.10.2590] [PMID: 9184206]
[48]
Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL, Clayton C. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol Microbiol 2000; 35(3): 542-52.
[http://dx.doi.org/10.1046/j.1365-2958.2000.01721.x] [PMID: 10672177]
[49]
Tovar J, Cunningham ML, Smith AC, Croft SL, Fairlamb AH. Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: effect on parasite intracellular survival. Proc Natl Acad Sci USA 1998; 95(9): 5311-6.
[http://dx.doi.org/10.1073/pnas.95.9.5311] [PMID: 9560272]
[50]
Tovar J, Wilkinson S, Mottram JC, Fairlamb AH. Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus. Mol Microbiol 1998; 29(2): 653-60.
[http://dx.doi.org/10.1046/j.1365-2958.1998.00968.x] [PMID: 9720880]
[51]
Beltran-Hortelano I, Perez-Silanes S, Galiano S. Trypanothione reductase and superoxide dismutase as current drug targets for trypanosoma cruzi: an overview of compounds with activity against Chagas disease. Curr Med Chem 2017; 24(11): 1066-138.
[http://dx.doi.org/10.2174/0929867323666161227094049] [PMID: 28025938]
[52]
Bernardes LS, Zani CL, Carvalho I. Trypanosomatidae diseases: from the current therapy to the efficacious role of trypanothione reductase in drug discovery. Curr Med Chem 2013; 20(21): 2673-96.
[http://dx.doi.org/10.2174/0929867311320210005] [PMID: 23410156]
[53]
Leroux AE, Krauth-Siegel RL. Thiol redox biology of trypanosomatids and potential targets for chemotherapy. Mol Biochem Parasitol 2016; 206(1-2): 67-74.
[http://dx.doi.org/10.1016/j.molbiopara.2015.11.003] [PMID: 26592324]
[54]
Castro H, Sousa C, Novais M, et al. Two linked genes of Leishmania infantum encode tryparedoxins localised to cytosol and mitochondrion. Mol Biochem Parasitol 2004; 136(2): 137-47.
[http://dx.doi.org/10.1016/j.molbiopara.2004.02.015] [PMID: 15478793]
[55]
Wilkinson SR, Horn D, Prathalingam SR, Kelly JM. RNA interference identifies two hydroperoxide metabolizing enzymes that are essential to the bloodstream form of the african trypanosome. J Biol Chem 2003; 278(34): 31640-6.
[http://dx.doi.org/10.1074/jbc.M303035200] [PMID: 12791697]
[56]
Castro H, Romao S, Carvalho S, Teixeira F, Sousa C, Tomás AM. Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity. PLoS One 2010; 5(9): e12607.
[http://dx.doi.org/10.1371/journal.pone.0012607] [PMID: 20838623]
[57]
El-Sayed NM, Myler PJ, Bartholomeu DC, et al. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 2005; 309(5733): 409-15.
[http://dx.doi.org/10.1126/science.1112631] [PMID: 16020725]
[58]
Piñeyro MD, Parodi-Talice A, Portela M, Arias DG, Guerrero SA, Robello C. Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin 1. J Proteomics 2011; 74(9): 1683-92.
[http://dx.doi.org/10.1016/j.jprot.2011.04.006] [PMID: 21539948]
[59]
Arias DG, Marquez VE, Chiribao ML, et al. Redox metabolism in Trypanosoma cruzi: functional characterization of tryparedoxins revisited. Free Radic Biol Med 2013; 63: 65-77.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.04.036] [PMID: 23665397]
[60]
Castro H, Tomas AM. Peroxidases of trypanosomatids. Antioxidants redox signaling 2008; 10(9): 1593-606.
[http://dx.doi.org/10.1089/ars.2008.2050]
[61]
Hofmann B, Budde H, Bruns K, et al. Structures of tryparedoxins revealing interaction with trypanothione. Biol Chem 2001; 382(3): 459-71.
[http://dx.doi.org/10.1515/BC.2001.056] [PMID: 11347894]
[62]
Guerrero SA, Montemartini M, Spallek R, et al. Cloning and expression of tryparedoxin I from Crithidia fasciculata. Biofactors 2000; 11(1-2): 67-9.
[http://dx.doi.org/10.1002/biof.5520110119] [PMID: 10705964]
[63]
Montemartini M, Nogoceke E, Gommel DU, et al. Tryparedoxin and tryparedoxin peroxidase. Biofactors 2000; 11(1-2): 71-2.
[http://dx.doi.org/10.1002/biof.5520110120] [PMID: 10705965]
[64]
Kalisz HM, Hofmann B, Nogoceke E, Gommel DU, Flohé L, Hecht HJ. Crystallisation of tryparedoxin I from Crithidia fasciculata. Biofactors 2000; 11(1-2): 73-5.
[http://dx.doi.org/10.1002/biof.5520110121] [PMID: 10705966]
[65]
Fiorillo A, Colotti G, Boffi A, Baiocco P, Ilari A. The crystal structures of the tryparedoxin-tryparedoxin peroxidase couple unveil the structural determinants of Leishmania detoxification pathway. PLoS Negl Trop Dis 2012; 6(8): e1781.
[http://dx.doi.org/10.1371/journal.pntd.0001781] [PMID: 22928053]
[66]
Budde H, Flohé L, Hecht HJ, et al. Kinetics and redox-sensitive oligomerisation reveal negative subunit cooperativity in tryparedoxin peroxidase of Trypanosoma brucei brucei. Biol Chem 2003; 384(4): 619-33.
[http://dx.doi.org/10.1515/BC.2003.069] [PMID: 12751791]
[67]
Flohé L, Steinert P, Hecht HJ, Hofmann B. Tryparedoxin and tryparedoxin peroxidase. Methods Enzymol 2002; 347: 244-58.
[http://dx.doi.org/10.1016/S0076-6879(02)47024-3] [PMID: 11898414]
[68]
Reckenfelderbäumer N, Krauth-Siegel RL. Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J Biol Chem 2002; 277(20): 17548-55.
[http://dx.doi.org/10.1074/jbc.M112115200] [PMID: 11867629]
[69]
Fraser-L’Hostis C, Defrise-Quertain F, Coral D, Deshusses J. Regulation of the intracellular pH in the protozoan parasite Trypanosoma brucei brucei. Biol Chem 1997; 378(9): 1039-46.
[PMID: 9348114]
[70]
Van Der Heyden N, Docampo R. Intracellular pH in mammalian stages of Trypanosoma cruzi is K+-dependent and regulated by H+-ATPases. Mol Biochem Parasitol 2000; 105(2): 237-51.
[http://dx.doi.org/10.1016/S0166-6851(99)00184-X] [PMID: 10693746]
[71]
Leroux AE, Haanstra JR, Bakker BM, Krauth-Siegel RL. Dissecting the catalytic mechanism of Trypanosoma brucei trypanothione synthetase by kinetic analysis and computational modeling. J Biol Chem 2013; 288(33): 23751-64.
[http://dx.doi.org/10.1074/jbc.M113.483289] [PMID: 23814051]
[72]
Lüdemann H, Dormeyer M, Sticherling C, Stallmann D, Follmann H, Krauth-Siegel RL. Trypanosoma brucei tryparedoxin, a thioredoxin-like protein in African trypanosomes. FEBS Lett 1998; 431(3): 381-5.
[http://dx.doi.org/10.1016/S0014-5793(98)00793-5] [PMID: 9714547]
[73]
Manta B, Comini M, Medeiros A, Hugo M, Trujillo M, Radi R. Trypanothione: a unique bis-glutathionyl derivative in trypanosomatids. Biochim Biophys Acta 2013; 1830(5): 3199-216.
[http://dx.doi.org/10.1016/j.bbagen.2013.01.013] [PMID: 23396001]
[74]
Lillig CH, Berndt C, Holmgren A. Glutaredoxin systems. Biochim Biophys Acta 2008; 1780(11): 1304-17.
[http://dx.doi.org/10.1016/j.bbagen.2008.06.003] [PMID: 18621099]
[75]
González-Chávez Z, Olin-Sandoval V, Rodíguez-Zavala JS, Moreno-Sánchez R, Saavedra E. Metabolic control analysis of the Trypanosoma cruzi peroxide detoxification pathway identifies tryparedoxin as a suitable drug target. Biochim Biophys Acta 2015; 1850(2): 263-73.
[http://dx.doi.org/10.1016/j.bbagen.2014.10.029] [PMID: 25450181]
[76]
Castro H, Romao S, Gadelha FR, Tomás AM. Leishmania infantum: provision of reducing equivalents to the mitochondrial tryparedoxin/tryparedoxin peroxidase system. Exp Parasitol 2008; 120(4): 421-3.
[http://dx.doi.org/10.1016/j.exppara.2008.09.002] [PMID: 18809403]
[77]
Piñeyro MD, Arcari T, Robello C, Radi R, Trujillo M. Tryparedoxin peroxidases from Trypanosoma cruzi: high efficiency in the catalytic elimination of hydrogen peroxide and peroxynitrite. Arch Biochem Biophys 2011; 507(2): 287-95.
[http://dx.doi.org/10.1016/j.abb.2010.12.014] [PMID: 21167808]
[78]
Schlecker T, Schmidt A, Dirdjaja N, Voncken F, Clayton C, Krauth-Siegel RL. Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei. J Biol Chem 2005; 280(15): 14385-94.
[http://dx.doi.org/10.1074/jbc.M413338200] [PMID: 15664987]
[79]
Trujillo M, Ferrer-Sueta G, Thomson L, Flohé L, Radi R. Kinetics of peroxiredoxins and their role in the decomposition of peroxynitrite. Subcell Biochem 2007; 44: 83-113.
[http://dx.doi.org/10.1007/978-1-4020-6051-9_5] [PMID: 18084891]
[80]
Krauth-Siegel RL, Schmidt H. Trypanothione and tryparedoxin in ribonucleotide reduction. Methods Enzymol 2002; 347: 259-66.
[http://dx.doi.org/10.1016/S0076-6879(02)47025-5] [PMID: 11898415]
[81]
Onn I, Kapeller I, Abu-Elneel K, Shlomai J. Binding of the universal minicircle sequence binding protein at the kinetoplast DNA replication origin. J Biol Chem 2006; 281(49): 37468-76.
[http://dx.doi.org/10.1074/jbc.M606374200] [PMID: 17046830]
[82]
Onn I, Milman-Shtepel N, Shlomai J. Redox potential regulates binding of universal minicircle sequence binding protein at the kinetoplast DNA replication origin. Eukaryot Cell 2004; 3(2): 277-87.
[http://dx.doi.org/10.1128/EC.3.2.277-287.2004] [PMID: 15075258]
[83]
Sela D, Shlomai J. Regulation of UMSBP activities through redox-sensitive protein domains. Nucleic Acids Res 2009; 37(1): 279-88.
[http://dx.doi.org/10.1093/nar/gkn927] [PMID: 19039000]
[84]
Arias DG, Piñeyro MD, Iglesias AA, Guerrero SA, Robello C. Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin II. J Proteomics 2015; 120: 95-104.
[http://dx.doi.org/10.1016/j.jprot.2015.03.001] [PMID: 25765699]
[85]
Dias L, Peloso EF, Leme AFP, et al. Trypanosoma cruzi tryparedoxin II interacts with different peroxiredoxins under physiological and oxidative stress conditions. Exp Parasitol 2018; 184: 1-10.
[http://dx.doi.org/10.1016/j.exppara.2017.10.015] [PMID: 29162347]
[86]
Comini MA, Krauth-Siegel RL, Flohé L. Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes. Biochem J 2007; 402(1): 43-9.
[http://dx.doi.org/10.1042/BJ20061341] [PMID: 17040206]
[87]
Romao S, Castro H, Sousa C, Carvalho S, Tomás AM. The cytosolic tryparedoxin of Leishmania infantum is essential for parasite survival. Int J Parasitol 2009; 39(6): 703-11.
[http://dx.doi.org/10.1016/j.ijpara.2008.11.009] [PMID: 19135056]
[88]
González-Chávez Z, Vázquez C, Mejia-Tlachi M, et al. Gamma-glutamylcysteine synthetase and tryparedoxin 1 exert high control on the antioxidant system in Trypanosoma cruzi contributing to drug resistance and infectivity. Redox Biol 2019; 26: 101231.
[http://dx.doi.org/10.1016/j.redox.2019.101231] [PMID: 31203195]
[89]
Fueller F, Jehle B, Putzker K, Lewis JD, Krauth-Siegel RL. High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin. J Biol Chem 2012; 287(12): 8792-802.
[http://dx.doi.org/10.1074/jbc.M111.338285] [PMID: 22275351]
[90]
Gretes MC, Poole LB, Karplus PA. Peroxiredoxins in parasites Antioxidants Redox Signal 2012; 17(4): 608-33.
[http://dx.doi.org/10.1089/ars.2011.4404]
[91]
Wood ZA, Schröder E, Robin Harris J, Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 2003; 28(1): 32-40.
[http://dx.doi.org/10.1016/S0968-0004(02)00003-8] [PMID: 12517450]
[92]
Perkins A, Nelson KJ, Parsonage D, Poole LB, Karplus PA. Peroxiredoxins: guardians against oxidative stress and modulators of peroxide signaling. Trends Biochem Sci 2015; 40(8): 435-45.
[http://dx.doi.org/10.1016/j.tibs.2015.05.001] [PMID: 26067716]
[93]
Piñeyro MD, Pizarro JC, Lema F, et al. Crystal structure of the tryparedoxin peroxidase from the human parasite Trypanosoma cruzi. J Struct Biol 2005; 150(1): 11-22.
[http://dx.doi.org/10.1016/j.jsb.2004.12.005] [PMID: 15797726]
[94]
Flohé L, Budde H, Bruns K, et al. Tryparedoxin peroxidase of Leishmania donovani: molecular cloning, heterologous expression, specificity, and catalytic mechanism. Arch Biochem Biophys 2002; 397(2): 324-35.
[http://dx.doi.org/10.1006/abbi.2001.2688] [PMID: 11795890]
[95]
Montemartini M, Kalisz HM, Hecht HJ, Steinert P, Flohé L. Activation of active-site cysteine residues in the peroxiredoxin-type tryparedoxin peroxidase of Crithidia fasciculata. Eur J Biochem 1999; 264(2): 516-24.
[http://dx.doi.org/10.1046/j.1432-1327.1999.00656.x] [PMID: 10491099]
[96]
Castro H, Budde H, Flohé L, et al. Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum. Free Radic Biol Med 2002; 33(11): 1563-74.
[http://dx.doi.org/10.1016/S0891-5849(02)01088-2] [PMID: 12446214]
[97]
Diechtierow M, Krauth-Siegel RL. A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage. Free Radic Biol Med 2011; 51(4): 856-68.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.05.014] [PMID: 21640819]
[98]
König J, Fairlamb AH. A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major. FEBS J 2007; 274(21): 5643-58.
[http://dx.doi.org/10.1111/j.1742-4658.2007.06087.x] [PMID: 17922848]
[99]
Trujillo M, Budde H, Piñeyro MD, et al. Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically detoxify peroxynitrite via oxidation of fast reacting thiols. J Biol Chem 2004; 279(33): 34175-82.
[http://dx.doi.org/10.1074/jbc.M404317200] [PMID: 15155760]
[100]
Castro H, Sousa C, Santos M, Cordeiro-da-Silva A, Flohé L, Tomás AM. Complementary antioxidant defense by cytoplasmic and mitochondrial peroxiredoxins in Leishmania infantum. Free Radic Biol Med 2002; 33(11): 1552-62.
[http://dx.doi.org/10.1016/S0891-5849(02)01089-4] [PMID: 12446213]
[101]
Levick MP, Tetaud E, Fairlamb AH, Blackwell JM. Identification and characterisation of a functional peroxidoxin from Leishmania major. Mol Biochem Parasitol 1998; 96(1-2): 125-37.
[http://dx.doi.org/10.1016/S0166-6851(98)00122-4] [PMID: 9851612]
[102]
Lopez JA, Carvalho TU, de Souza W, et al. Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi. Free Radic Biol Med 2000; 28(5): 767-72.
[http://dx.doi.org/10.1016/S0891-5849(00)00159-3] [PMID: 10754272]
[103]
Tetaud E, Giroud C, Prescott AR, et al. Molecular characterisation of mitochondrial and cytosolic trypanothione-dependent tryparedoxin peroxidases in Trypanosoma brucei. Mol Biochem Parasitol 2001; 116(2): 171-83.
[http://dx.doi.org/10.1016/S0166-6851(01)00320-6] [PMID: 11522350]
[104]
Lin YC, Hsu JY, Chiang SC, Lee ST. Distinct overexpression of cytosolic and mitochondrial tryparedoxin peroxidases results in preferential detoxification of different oxidants in arsenite-resistant Leishmania amazonensis with and without DNA amplification. Mol Biochem Parasitol 2005; 142(1): 66-75.
[http://dx.doi.org/10.1016/j.molbiopara.2005.03.009] [PMID: 15907561]
[105]
Trujillo M, Ferrer-Sueta G, Radi R. Peroxynitrite detoxification and its biologic implications. Antioxidants redox signaling 2008; 10(9): 1607-20.
[http://dx.doi.org/10.1089/ars.2008.2060]
[106]
Piacenza L, Peluffo G, Alvarez MN, Kelly JM, Wilkinson SR, Radi R. Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously-derived peroxynitrite. Biochem J 2008; 410(2): 359-68.
[http://dx.doi.org/10.1042/BJ20071138] [PMID: 17973627]
[107]
Piñeyro MD, Arias D, Ricciardi A, Robello C, Parodi-Talice A. Oligomerization dynamics and functionality of Trypanosoma cruzi cytosolic tryparedoxin peroxidase as peroxidase and molecular chaperone. Biochim Biophys Acta, Gen Subj 2019; 1863(10): 1583-94.
[http://dx.doi.org/10.1016/j.bbagen.2019.06.013] [PMID: 31265897]
[108]
Jang HH, Lee KO, Chi YH, et al. Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell 2004; 117(5): 625-35.
[http://dx.doi.org/10.1016/j.cell.2004.05.002] [PMID: 15163410]
[109]
Castro H, Teixeira F, Romao S, et al. Leishmania mitochondrial peroxiredoxin plays a crucial peroxidase-unrelated role during infection: insight into its novel chaperone activity. PLoS Pathog 2011; 7(10): e1002325.
[http://dx.doi.org/10.1371/journal.ppat.1002325] [PMID: 22046130]
[110]
Piñeyro MD, Parodi-Talice A, Arcari T, Robello C. Peroxiredoxins from Trypanosoma cruzi: virulence factors and drug targets for treatment of Chagas disease? Gene 2008; 408(1-2): 45-50.
[http://dx.doi.org/10.1016/j.gene.2007.10.014] [PMID: 18022330]
[111]
Iyer JP, Kaprakkaden A, Choudhary ML, Shaha C. Crucial role of cytosolic tryparedoxin peroxidase in Leishmania donovani survival, drug response and virulence. Mol Microbiol 2008; 68(2): 372-91.
[http://dx.doi.org/10.1111/j.1365-2958.2008.06154.x] [PMID: 18312262]
[112]
Das S, Giri S, Sundar S, Shaha C. Functional Involvement of Leishmania donovani tryparedoxin peroxidases during infection and drug treatment. Antimicrob Agents Chemother 2017; 62(1): e00806-17.
[http://dx.doi.org/10.1128/AAC.00806-17] [PMID: 29061756]
[113]
Brindisi M, Brogi S, Relitti N, et al. Structure-based discovery of the first non-covalent inhibitors of Leishmania major tryparedoxin peroxidase by high throughput docking. Sci Rep 2015; 5: 9705.
[http://dx.doi.org/10.1038/srep09705] [PMID: 25951439]
[114]
Berná L, Rodriguez M, Chiribao ML, et al. Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi. Microb Genom 2018; 4(5)
[http://dx.doi.org/10.1099/mgen.0.000177] [PMID: 29708484]
[115]
Schmidt H, Krauth-Siegel RL. Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei. J Biol Chem 2003; 278(47): 46329-36.
[http://dx.doi.org/10.1074/jbc.M305338200] [PMID: 12949079]
[116]
Schmidt A, Clayton CE, Krauth-Siegel RL. Silencing of the thioredoxin gene in Trypanosoma brucei brucei. Mol Biochem Parasitol 2002; 125(1-2): 207-10.
[http://dx.doi.org/10.1016/S0166-6851(02)00215-3] [PMID: 12467989]
[117]
Reckenfelderbäumer N, Lüdemann H, Schmidt H, Steverding D, Krauth-Siegel RL. Identification and functional characterization of thioredoxin from Trypanosoma brucei brucei. J Biol Chem 2000; 275(11): 7547-52.
[http://dx.doi.org/10.1074/jbc.275.11.7547] [PMID: 10713060]
[118]
Piattoni CV, Blancato VS, Miglietta H, Iglesias AA, Guerrero SA. On the occurrence of thioredoxin in Trypanosoma cruzi. Acta Trop 2006; 97(2): 151-60.
[http://dx.doi.org/10.1016/j.actatropica.2005.10.005] [PMID: 16310752]
[119]
Currier RB, Ulrich K, Leroux AE, et al. An essential thioredoxin-type protein of Trypanosoma brucei acts as redox-regulated mitochondrial chaperone. PLoS Pathog 2019; 15(9): e1008065.
[http://dx.doi.org/10.1371/journal.ppat.1008065] [PMID: 31557263]
[120]
Wilkinson SR, Meyer DJ, Kelly JM. Biochemical characterization of a trypanosome enzyme with glutathione-dependent peroxidase activity. Biochem J 2000; 352(Pt 3): 755-61.
[http://dx.doi.org/10.1042/bj3520755] [PMID: 11104683]
[121]
Wilkinson SR, Taylor MC, Touitha S, Mauricio IL, Meyer DJ, Kelly JM. TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum. Biochem J 2002; 364(Pt 3): 787-94.
[http://dx.doi.org/10.1042/bj20020038] [PMID: 12049643]
[122]
Schlecker T, Comini MA, Melchers J, Ruppert T, Krauth-Siegel RL. Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei. Biochem J 2007; 405(3): 445-54.
[http://dx.doi.org/10.1042/BJ20070259] [PMID: 17456049]
[123]
Wilkinson SR, Obado SO, Mauricio IL, Kelly JM. Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum. Proc Natl Acad Sci USA 2002; 99(21): 13453-8.
[http://dx.doi.org/10.1073/pnas.202422899] [PMID: 12351682]
[124]
Hugo M, Martínez A, Trujillo M, et al. Kinetics, subcellular localization, and contribution to parasite virulence of a Trypanosoma cruzi hybrid type A heme peroxidase (TcAPx-CcP). Proc Natl Acad Sci USA 2017; 114(8): E1326-35.
[http://dx.doi.org/10.1073/pnas.1618611114] [PMID: 28179568]
[125]
Taylor MC, Lewis MD, Fortes Francisco A, Wilkinson SR, Kelly JM. The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against oxidative stress but is not a determinant of virulence. PLoS Negl Trop Dis 2015; 9(4): e0003707.
[http://dx.doi.org/10.1371/journal.pntd.0003707] [PMID: 25875298]
[126]
Adak S, Datta AK. Leishmania major encodes an unusual peroxidase that is a close homologue of plant ascorbate peroxidase: a novel role of the transmembrane domain. Biochem J 2005; 390(Pt 2): 465-74.
[http://dx.doi.org/10.1042/BJ20050311] [PMID: 15850459]
[127]
Pal S, Dolai S, Yadav RK, Adak S. Ascorbate peroxidase from Leishmania major controls the virulence of infective stage of promastigotes by regulating oxidative stress. PLoS One 2010; 5(6): e11271.
[http://dx.doi.org/10.1371/journal.pone.0011271] [PMID: 20585663]
[128]
Xiang L, Laranjeira-Silva MF, Maeda FY, Hauzel J, Andrews NW, Mittra B. Ascorbate-Dependent Peroxidase (APX) from leishmania amazonensis is a reactive oxygen species-induced Essential enzyme that regulates virulence. Infect Immun 2019; 87(12): e00193-19.
[http://dx.doi.org/10.1128/IAI.00193-19] [PMID: 31527128]
[129]
Ströher E, Millar AH. The biological roles of glutaredoxins. Biochem J 2012; 446(3): 333-48.
[http://dx.doi.org/10.1042/BJ20112131] [PMID: 22928493]
[130]
Lillig CH, Berndt C. Glutaredoxins in thiol/disulfide exchange Antioxidants redox signaling 2013; 18(13): 1654-65.
[131]
Rouhier N, Lemaire SD, Jacquot JP. The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation. Annu Rev Plant Biol 2008; 59: 143-66.
[http://dx.doi.org/10.1146/annurev.arplant.59.032607.092811] [PMID: 18444899]
[132]
Herrero E, de la Torre-Ruiz MA. Monothiol glutaredoxins: a common domain for multiple functions. Cell Mol Life Sci 2007; 64(12): 1518-30.
[http://dx.doi.org/10.1007/s00018-007-6554-8] [PMID: 17415523]
[133]
Ceylan S, Seidel V, Ziebart N, Berndt C, Dirdjaja N, Krauth-Siegel RL. The dithiol glutaredoxins of african trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism. J Biol Chem 2010; 285(45): 35224-37.
[http://dx.doi.org/10.1074/jbc.M110.165860] [PMID: 20826822]
[134]
Márquez VE, Arias DG, Chiribao ML, et al. Redox metabolism in Trypanosoma cruzi. Biochemical characterization of dithiol glutaredoxin dependent cellular pathways. Biochimie 2014; 106: 56-67.
[http://dx.doi.org/10.1016/j.biochi.2014.07.027] [PMID: 25110158]
[135]
Marquez VE, Arias DG, Piattoni CV, Robello C, Iglesias AA, Guerrero SA. Cloning, expression, and characterization of a dithiol glutaredoxin from Trypanosoma cruzi Antioxidants redox signaling 2010; 12(6): 787-92.
[http://dx.doi.org/10.1089/ars.2009.2907]
[136]
Ebersoll S, Musunda B, Schmenger T, et al. A glutaredoxin in the mitochondrial intermembrane space has stage-specific functions in the thermo-tolerance and proliferation of African trypanosomes. Redox Biol 2018; 15: 532-47.
[http://dx.doi.org/10.1016/j.redox.2018.01.011] [PMID: 29413965]
[137]
Comini MA, Rettig J, Dirdjaja N, Hanschmann EM, Berndt C, Krauth-Siegel RL. Monothiol glutaredoxin-1 is an essential iron-sulfur protein in the mitochondrion of African trypanosomes. J Biol Chem 2008; 283(41): 27785-98.
[http://dx.doi.org/10.1074/jbc.M802010200] [PMID: 18669638]
[138]
Manta B, Pavan C, Sturlese M, et al. Iron-sulfur cluster binding by mitochondrial monothiol glutaredoxin-1 of Trypanosoma brucei: molecular basis of iron-sulfur cluster coordination and relevance for parasite infectivity Antioxidants Redox Signaling 2013; 19(7): 665-82.
[139]
Marchese L, Nascimento JF, Damasceno FS, Bringaud F, Michels PAM, Silber AM. The uptake and metabolism of amino acids, and their unique role in the biology of pathogenic trypanosomatids. Pathogens 2018; 7(2): E36.
[http://dx.doi.org/10.3390/pathogens7020036] [PMID: 29614775]
[140]
Boschi-Muller S, Gand A, Branlant G. The methionine sulfoxide reductases: Catalysis and substrate specificities. Arch Biochem Biophys 2008; 474(2): 266-73.
[http://dx.doi.org/10.1016/j.abb.2008.02.007] [PMID: 18302927]
[141]
Stadtman ER. Cyclic oxidation and reduction of methionine residues of proteins in antioxidant defense and cellular regulation. Arch Biochem Biophys 2004; 423(1): 2-5.
[http://dx.doi.org/10.1016/j.abb.2003.10.001] [PMID: 14989257]
[142]
Jiang B, Moskovitz J. The functions of the mammalian methionine sulfoxide reductase system and related diseases. Antioxidants 2018; 7(9): E122.
[http://dx.doi.org/10.3390/antiox7090122] [PMID: 30231496]
[143]
Sansom FM, Tang L, Ralton JE, Saunders EC, Naderer T, McConville MJ. Leishmania major methionine sulfoxide reductase A is required for resistance to oxidative stress and efficient replication in macrophages. PLoS One 2013; 8(2): e56064.
[http://dx.doi.org/10.1371/journal.pone.0056064] [PMID: 23437085]
[144]
Arias DG, Cabeza MS, Erben ED, et al. Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp. Free Radic Biol Med 2011; 50(1): 37-46.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.695] [PMID: 20969952]
[145]
Guerrero SA, Arias DG, Cabeza MS, et al. Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei. Free Radic Biol Med 2017; 112: 524-33.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.023] [PMID: 28865997]
[146]
Arias DG, Cabeza MS, Echarren ML, et al. On the functionality of a methionine sulfoxide reductase B from Trypanosoma cruzi. Free Radic Biol Med 2020; 158: 96-114.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.06.035] [PMID: 32682073]
[147]
Mesías AC, Garg NJ, Zago MP. Redox balance keepers and possible cell functions managed by redox homeostasis in trypanosoma cruzi. Front Cell Infect Microbiol 2019; 9: 435.
[http://dx.doi.org/10.3389/fcimb.2019.00435] [PMID: 31921709]
[148]
de Jesus TC, Nunes VS, Lopes Mde C, et al. Chromatin proteomics reveals variable histone modifications during the life cycle of Trypanosoma cruzi. J Proteome Res 2016; 15(6): 2039-51.
[http://dx.doi.org/10.1021/acs.jproteome.6b00208] [PMID: 27108550]
[149]
Parodi-Talice A, Monteiro-Goes V, Arrambide N, et al. Proteomic analysis of metacyclic trypomastigotes undergoing Trypanosoma cruzi metacyclogenesis. J Mass Spectrom 2007; 42(11): 1422-32.
[http://dx.doi.org/10.1002/jms.1267] [PMID: 17960573]
[150]
Zago MP, Hosakote YM, Koo SJ, et al. TcI isolates of Trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice. Infect Immun 2016; 84(6): 1842-56.
[http://dx.doi.org/10.1128/IAI.00193-16] [PMID: 27068090]
[151]
Molina I, Gómez i Prat J, Salvador F, et al. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med 2014; 370(20): 1899-908.
[http://dx.doi.org/10.1056/NEJMoa1313122] [PMID: 24827034]
[152]
Chatelain E, Ioset JR. Drug discovery and development for neglected diseases: the DNDi model. Drug Des Devel Ther 2011; 5: 175-81.
[PMID: 21552487]
[153]
Bhattacharya A, Corbeil A, do Monte-Neto RL, Fernandez-Prada C. Of drugs and trypanosomatids: New tools and knowledge to reduce bottlenecks in drug discovery. Genes (Basel) 2020; 11(7): E722.
[http://dx.doi.org/10.3390/genes11070722] [PMID: 32610603]
[154]
Patterson S, Alphey MS, Jones DC, et al. Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography. J Med Chem 2011; 54(19): 6514-30.
[http://dx.doi.org/10.1021/jm200312v] [PMID: 21851087]
[155]
Persch E, Bryson S, Todoroff NK, et al. Binding to large enzyme pockets: small-molecule inhibitors of trypanothione reductase. ChemMedChem 2014; 9(8): 1880-91.
[http://dx.doi.org/10.1002/cmdc.201402032] [PMID: 24788386]
[156]
De Gasparo R, Halgas O, Harangozo D, et al. Targeting a large active site: structure-based design of Nano molar inhibitors of Trypanosoma brucei trypanothione reductase. Chemistry 2019; 25(49): 11416-21.
[http://dx.doi.org/10.1002/chem.201901664] [PMID: 31407832]
[157]
Saccoliti F, Angiulli G, Pupo G, et al. Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide derivatives. J Enzyme Inhib Med Chem 2017; 32(1): 304-10.
[http://dx.doi.org/10.1080/14756366.2016.1250755] [PMID: 28098499]
[158]
Ilari A, Baiocco P, Messori L, et al. A gold-containing drug against parasitic polyamine metabolism: the X-ray structure of trypanothione reductase from Leishmania infantum in complex with auranofin reveals a dual mechanism of enzyme inhibition. Amino Acids 2012; 42(2-3): 803-11.
[http://dx.doi.org/10.1007/s00726-011-0997-9] [PMID: 21833767]
[159]
Lantwin CB, Schlichting I, Kabsch W, Pai EF, Krauth-Siegel RL. The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state. Proteins 1994; 18(2): 161-73.
[http://dx.doi.org/10.1002/prot.340180208] [PMID: 8159665]
[160]
Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WN. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 1999; 7(1): 81-9.
[http://dx.doi.org/10.1016/S0969-2126(99)80011-2] [PMID: 10368274]
[161]
Saravanamuthu A, Vickers TJ, Bond CS, Peterson MR, Hunter WN, Fairlamb AH. Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design. J Biol Chem 2004; 279(28): 29493-500.
[http://dx.doi.org/10.1074/jbc.M403187200] [PMID: 15102853]
[162]
Zhang Y, Bond CS, Bailey S, Cunningham ML, Fairlamb AH, Hunter WN. The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution Protein science: a publication of the Protein Society 1996; 5(1): 52-61.
[163]
Wagner A, Le TA, Brennich M, et al. Inhibitor-induced dimerization of an essential oxidoreductase from African trypanosomes. Angew Chem Int Ed Engl 2019; 58(11): 3640-4.
[http://dx.doi.org/10.1002/anie.201810470] [PMID: 30605929]
[164]
Motyka SA, Drew ME, Yildirir G, Englund PT. Overexpression of a cytochrome b5 reductase-like protein causes kinetoplast DNA loss in Trypanosoma brucei. J Biol Chem 2006; 281(27): 18499-506.
[http://dx.doi.org/10.1074/jbc.M602880200] [PMID: 16690608]
[165]
Teixeira F, Tse E, Castro H, et al. Chaperone activation and client binding of a 2-cysteine peroxiredoxin. Nat Commun 2019; 10(1): 659.
[http://dx.doi.org/10.1038/s41467-019-08565-8] [PMID: 30737390]
[166]
Friemann R, Schmidt H, Ramaswamy S, Forstner M, Krauth-Siegel RL, Eklund H. Structure of thioredoxin from Trypanosoma brucei brucei. FEBS Lett 2003; 554(3): 301-5.
[http://dx.doi.org/10.1016/S0014-5793(03)01173-6] [PMID: 14623083]
[167]
Patel S, Hussain S, Harris R, et al. Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I). Biochem J 2010; 425(3): 513-22.
[http://dx.doi.org/10.1042/BJ20091167] [PMID: 19886864]
[168]
Melchers J, Diechtierow M, Fehér K, et al. Structural basis for a distinct catalytic mechanism in Trypanosoma brucei tryparedoxin peroxidase. J Biol Chem 2008; 283(44): 30401-11.
[http://dx.doi.org/10.1074/jbc.M803563200] [PMID: 18684708]
[169]
Schaffroth C, Bogacz M, Dirdjaja N, Nißen A, Krauth-Siegel RL. The cytosolic or the mitochondrial glutathione peroxidase-type tryparedoxin peroxidase is sufficient to protect procyclic Trypanosoma brucei from iron-mediated mitochondrial damage and lysis. Mol Microbiol 2016; 99(1): 172-87.
[http://dx.doi.org/10.1111/mmi.13223] [PMID: 26374473]
[170]
Yadav RK, Dolai S, Pal S, Adak S. Role of tryptophan-208 residue in cytochrome c oxidation by ascorbate peroxidase from Leishmania major-kinetic studies on Trp208Phe mutant and wild type enzyme. Biochim Biophys Acta 2008; 1784(5): 863-71.
[http://dx.doi.org/10.1016/j.bbapap.2008.02.006] [PMID: 18342641]

Rights & Permissions Print Cite
Article Metrics
51
1
World Health Day
© 2024 Bentham Science Publishers | Privacy Policy