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	Trypanothione - Wikipedia, the free encyclopedia
		Trypanothione is a unusual form of glutathione that is found in parasitic protozoa such as leishmania and trypanosomes (1).
		Trypanothione is not present in humans and is essential for the survival of the parasites.
		The parasite-specific trypanothione metabolism of trypanosoma and leishmania.
	en.wikipedia.org /wiki/Trypanothione (277 words)

	[No title] (Site not responding. Last check: 2007-10-17)
		5 : Q963S6_TRYCR 1.00 1.00 24 453 1 430 430 0 0 430 Q963S6 Trypanothione reductase (Fragment).
		19 : Q963S3_9TRYP 0.97 0.98 507 936 1 430 430 0 0 430 Q963S3 Trypanothione reductase (Fragment).
		20 : Q963S3_9TRYP 0.97 0.98 24 453 1 430 430 0 0 430 Q963S3 Trypanothione reductase (Fragment).
	www.infobiogen.fr /db/hssp/1aog.hssp (7271 words)

	Extrachromosomal, homologous expression of trypanothione reductase and its complementary mRNA in Trypanosoma cruzi -- ...
		Trypanothione reductase (TR), a flavoprotein oxidoreductase present in trypanosomatids but absent in human cells, is regarded as a potential target for the chemotherapy of several tropical parasitic diseases caused by trypanosomes and leishmanias.
		Together with its corresponding oxido-reductase, trypanothione reductase (TR), trypanothione is thought to fulfil important physiological functions including maintenance of a reduced intracellular environment and defense against heavy metals, oxidants and xenobiotics (4), roles ascribed to the glutathione system in most other organisms.
		Since the trypanothione system appears to be shared between most members of the trypanosomatid family it is likely that any rationally designed inhibitor of TR will be potentially useful in the treatment of a wide variety of parasitic diseases.
	nar.oxfordjournals.org /cgi/content/full/24/15/2942 (5259 words)

	Trypanothione: Facts and details from Encyclopedia Topic (Site not responding. Last check: 2007-10-17)
		Trypanothione is a unusual form of glutathione glutathione quick summary:
		Trypanothione contains two molecules of glutathione joined by a polyamine[Follow this hyperlink for a summary of this subject] linker.
		An enzyme (in greek en = in and zyme = leaven) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3d orientation...
	www.absoluteastronomy.com /encyclopedia/T/Tr/Trypanothione.htm (233 words)

	Memórias on line
		Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase.
		Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids.
		Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase.
	memorias.ioc.fiocruz.br /984/4782ref.html (519 words)

	Biological Chemistry - Abstract (Site not responding. Last check: 2007-10-17)
		The bis(glutathionyl)spermidine trypanothione exclusively occurs in parasitic protozoa of the order Kinetoplastida, such as trypanosomes and leishmania, some of which are the causative agents of several tropical diseases.
		Trypanothione is a reductant of thioredoxin and tryparedoxin, small dithiol proteins, which in turn deliver reducing equivalents for the synthesis of deoxyribonucleotides as well as for the detoxification of hydroperoxides by different peroxidases.
		Thus the trypanothione system is central for any thiol regeneration and trypanothione reductase has been shown to be an essential enzyme in these parasites.
	www.degruyter.de /journals/bc/abs/10474.html (220 words)

	Drug action (Site not responding. Last check: 2007-10-17)
		This pathway leasd to the formation of trypanothione, an adduct of two molecules of glutathione linked to the two terminal amino groups of spermidine, that is formed from ornithine after decarboxylation.
		This complex behaves as a potent inhibitor of the enzyme trypanothione reductase, preventing the reduction of oxidized trypanothione.
		The notion that many different drugs all act on the sensitivity of the parasites towards oxidative stress has lead to the perception that combination therapy, using two or more drugs, may lead to synergism, resulting in a superior effect with lower dosages of the drugs than would otherwise be required.
	www.icp.ucl.ac.be /~opperd/parasites/drug_act.htm (288 words)

	Bis(glutathionyl)spermine and Other Novel Trypanothione Analogues in Trypanosoma cruzi -- Ariyanayagam et al. 278 (30): ...
		In Trypanosoma cruzi, trypanothione is synthesized by an unusual
		is a physiological substrate of recombinant trypanothione reductase,
		and spermidine to trypanothione and all the subsequent reverse
	www.jbc.org /cgi/content/full/278/30/27612 (3766 words)

	Attenuated strains of leishmania and uses thereof - Patent 6652847
		Krauth-Siegel, R.L., Enders, B., Henderson, G.B., Fairlamb, A.H., and Schirmer, R.H. Trypanothione reductase from Trypanosome cruzi: purification and characterization of the crystalline enzymes.
		The gene contributing to the virulence of the strain in this aspect of the invention may be one expressed in both the promastigote and amastigote stages of the life cycle of the strain.
		A large portion of the trypanothione reductase (TR) coding region (85% of the TR gene from nucleotide 153 to 1406) from L. tarentolae, L. donovani donovani TR and L. major total DNAs was amplified by PCR using degenerated oligonucleotide primers derived from the L. donovani TR coding sequence (ref. 16).
	www.freepatentsonline.com /6652847.html (6002 words)

	AHF personal web page
		Trypanothione: a novel bis(glutathionyl)spermidine co-factor for glutathione reductase in trypanosomatids.
		Henderson, G.B., Fairlamb, A.H. and Cerami, A. Trypanothione dependent peroxide metabolism in Crithidia fasciculata and Trypanosoma brucei.
		Fairlamb, A.H. The role of glutathionylspermidine and trypanothione in regulation of intracellular spermidine levels during growth of Crithidia fasciculata.
	www.personal.dundee.ac.uk /~ahfairla (1462 words)

	Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction. (Site not responding. Last check: 2007-10-17)
		Glutathione reductase (EC 1.6.4.2; CAS registry number 9001-48-3) and trypanothione reductase (CAS registry number 102210-35-5), which are related flavoprotein disulfide oxidoreductases, have marked specificities for glutathione and trypanothione, respectively.
		However, the mutation of Ala-18, Asn-21, and Arg-22 to the amino acid residues (Glu, Trp, and Asn, respectively) in corresponding positions in Trypanosoma congolense trypanothione reductase confirmed that this region of polypeptide chain is intimately involved in substrate recognition.
		The mutation of Asn-21 to Arg demonstrated that this single change was insufficient to generate the greater discrimination against trypanothione shown by human glutathione reductase compared with the E. coli enzyme.
	www.ihop-net.org /UniPub/iHOP/gp/42416.html (232 words)

	And in this corner we have the the Reducer!
		Trypanothione reductase is a flavoprotein unique to pathogenic protozoans.
		Trypanothione, similar to human glutathione, is oxidized during this process of protecting the parasite from the damages of oxidative species.
		The trypanothione must then be brought back to its reduced state in order for it to perform its function again.
	www.chem.uwec.edu /Webpapers2001/thomaeam/Pages/TR.html (115 words)

	A Single Enzyme Catalyses Formation of Trypanothione from Glutathione and Spermidine in Trypanosoma cruzi -- Oza et al. ...
		The biosynthesis of trypanothione involves two metabolic pathways that are distinct in other organisms: i.e.
		Biosynthesis of trypanothione involves ATP-dependent conjugation of GSH to both primary amines of spermidine (19).
		Alignment of the predicted amino acid sequences of trypanothione synthetases and glutathionylspermidine synthetases.
	www.jbc.org /cgi/content/full/277/39/35853 (4545 words)

	Memórias on line
		The decrease in the absorbance at 340 nm was measured and initial rates determined using the first 10-20 sec of data, in such way that the correlation coefficient to a straight line was greater than 0.95.
		Thus, even though trypanothione disulphide levels would be expected to increase in cells due to the metabolic roles of trypanothione as an antioxidant and as an electron donor for reduction of ribonucleotides, the level of inhibition of trypanothione reductase would remain constant.
		As discussed above, such inhibitors suffer from the disadvantage that their inhibitory effects are reversed by the accumulation of trypanothione disulphide.
	memorias.ioc.fiocruz.br /984/4782rd.html (709 words)

	Comparison of Resin and Solution Screening Methodologies in Combinatorial Chemistry and the Identification of a 100 nM ...
		Potent inhibitors (100 nM) of trypanothione reductase were identified both in the solution screen and in the resin-based screens when using the PEGA resin of Meldal.
		Clearly there is consensus between the three screening methods: all identified Arg in one position and an aromatic residue in the second, although the nature of this second group varied.
		The identification of a 100 nM inhibitor of trypanothione reductase is a good starting point for future optimization studies and the most potent inhibitor to date.
	pubs.acs.org /cgi-bin/jtextd?jcchff/asap/html/cc990013c.html (4393 words)

	Phenotype of recombinant Leishmania donovani and Trypanosoma cruzi which over-express trypanothione reductase. ... (Site not responding. Last check: 2007-10-17)
		Phenotype of recombinant Leishmania donovani and Trypanosoma cruzi which over-express trypanothione reductase.
		Trypanothione reductase is thought to be important in maintaining an
		Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: Effect on parasite intracellular survival
	content.febsjournal.org /cgi/content/abstract/218/1/29 (519 words)

	Structural studies of glutathione reductase family
		Aboagye-Kwarteng, T., Smith, K. and Fairlamb, A.H. Molecular characterization of the trypanothione reductase gene from Crithidia fasciculata and Trypanosoma brucei: comparison with other flavoprotein disulphide oxidoreductases with respect to substrate specificity and catalytic mechanism.
		Cunningham, M.L., Zvelebil, M.J. and Fairlamb, A.H. Mechanism of inhibition of trypanothione reductase and glutathione reductase by trivalent organic arsenicals.
		Sullivan, F.X., Sobolov, S.B., Bradley, M. and Walsh, C.T. Mutational analysis of parasite trypanothione reductase: acquisition of glutathione reductase activity in a triple mutant.
	p450.abc.hu /GR_reviews.html (1734 words)

	IngentaConnect The Battle against Trypanosomiasis and Leishmaniasis: Metal-based... (Site not responding. Last check: 2007-10-17)
		Trypanothione reductase is an enzyme that is unique to organisms belonging to the family Trypanosomatidae.
		Trypanothione reductase plays a pivotal role in maintaining the redox balance of trypanosomatids, thus the development of inhibitors of trypanothione reductase may lead to the design of new drugs to combat diseases caused by parasitic trypanosomatids.
		In this review, the major diseases caused by Trypanosomatidae, current drugs, drug resistance, and an overview of trypanothione and trypanothione reductase are summarized.
	www.ingentaconnect.com /content/ben/cmcaia/2005/00000004/00000004/art00005 (339 words)

	Current Pharmaceutical Design, Volume 7, No. 12, 2001
		Trypanothione is the key molecule in the defence mechanism of Trypanosoma and Leishmania against oxidative stress.
		The uniqueness of trypanothione makes the metabolism of this molecule an attractive target in antitrypanosomal and antileishmanial drug design.
		The following targets and their respective inhibitors will be discussed: biosynthesis of trypanothione with glutathionylspermidine synthetase and trypanothione synthetase; biosynthesis of glutathione with g-glutamylcysteine synthetase; biosynthesis of spermidine with ornithine decarboxylase; trypanothione hydroperoxide metabolism with tryparedoxine peroxidase, tryparedoxine and trypanothione reductase.
	www.bentham.org /cpd/contabs/cpd7-12.htm (912 words)

	2002 Molecular Parasitology Meeting: Abstract Book Online (Site not responding. Last check: 2007-10-17)
		Polyamine metabolism in Trypanosoma cruzi epimastigotes varies from other trypanosomatids in that: (1) they are unable to synthesize putrescine de novo (2) they possess high affinity diamine and polyamine transporters (3) they are able to synthesize spermine (4) they can synthesize homotrypanothione in place of trypanothione when cadaverine or aminopropylcadaverine is available in the medium.
		Like trypanothione disulphide, bis(glutathionyl)spermine disulphide is a substrate for trypanothione reductase.
		We recently reported that synthesis of trypanothione is catalysed by an unusual trypanothione synthetase/amidase (TcTryS) that forms both glutathionylspermidine and trypanothione from glutathione and spermidine.
	www.mbl.edu /mpm/mpm-2002/abstracts/abstract.php?id=343 (274 words)

	Glutathione Reductase Turned into Trypanothione Reductase: Structural Analysis of an Engineered Change in Substrate ...
		Instead, they rely on trypanothione and trypanothione reductase to protect them from oxidative stress.
		Trypanothione reductase (TR) and the corresponding host enzyme, human red blood cell glutathione reductase (GR), belong to the same flavoprotein family.
		We have taken advantage of the ease with which ligand complexes can be produced in GR crystals, a property that extends to the isomorphous GRTR crystals, and have produced and analyzed crystals of GRTR complexes with glutathione, trypanothione, glutathionylspermidine and of a true catalytic intermediate, the mixed disulfide between trypanothione and the enzyme.
	pubs.acs.org /cgi-bin/abstract.cgi/bichaw/1997/36/i21/abs/bi963074p.html (388 words)

	Flavoprotein structure and mechanism. 5. Trypanothione reductase and lipoamide dehydrogenase as targets for a ...
		Trypanothione reductase and lipoamide dehydrogenase as targets for a structure-based drug design -- Krauth-Siegel and Schoneck 9 (12): 1138 -- The FASEB Journal
		Trypanothione reductase and lipoamide dehydrogenase as targets for a structure-based drug design
		Trypanothione reductase (TR) is a flavoenzyme that has been found only in
	www.fasebj.org /cgi/content/abstract/9/12/1138 (395 words)

	e-Prints Soton - Optimising inhibitors of trypanothione reductase using solid-phase chemistry
		Chitkul, B. and Bradley, M. Optimising inhibitors of trypanothione reductase using solid-phase chemistry.
		A series of inhibitors of the enzyme trypanothione reductase has been identified using directed solid-phase chemistry.
		The compounds were based on a series of polyamine scaffolds and used the natural product kukoamine A as the lead structure.
	eprints.soton.ac.uk /18942 (137 words)

	OCA Atlas for 1AOG (Site not responding. Last check: 2007-10-17)
		Trypanothione + nadp(+) = trypanothione disulfide + nadph.
		Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.
		The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution., Zhang Y, Bond CS, Bailey S, Cunningham ML, Fairlamb AH, Hunter WN, Protein Sci 1996 Jan;5(1):52-61.
	oca.ebi.ac.uk /oca-bin/ocashort?id=1AOG (404 words)

	Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania -- Mukhopadhyay et al. 93 ... (Site not responding. Last check: 2007-10-17)
		Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania -- Mukhopadhyay et al.
		Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania
		conjugated to trypanothione, and extruded by the As-thiol pump.
	intl.pnas.org /cgi/content/abstract/93/19/10383 (759 words)

	IngentaConnect Enzymes of the Trypanothione Metabolism as Targets for Antitrypan... (Site not responding. Last check: 2007-10-17)
		The dithiol trypanothione is the key molecule for the synthesis of DNA precursors, the homeostasis of ascorbate, the detoxification of hydroperoxides, and the sequestration / export of thiol conjugates.
		Synthesis and reduction of trypanothione are essential for the maintenance of a reducing intracellular milieu which renders the respective enzymes attractive drug target molecules.
		The most effective inhibitors of the enzymes known to date, their mode of action, and the (dis)advantages of different types of inhibitors as potential drug candidates will be discussed.
	www.ingentaconnect.com /content/ben/ctmc/2002/00000002/00000011/art00005 (278 words)

	Inhibition of Trypanothione Reductase by Substrate Analogues (Site not responding. Last check: 2007-10-17)
		Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites.
		TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development.
		Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T.
	pubs.acs.org /cgi-bin/abstract.cgi/orlef7/2000/2/i23/abs/ol0065423.html (99 words)

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