The reduced state of T[SH] 2 is maintained by NADPH-dependent trypanothione reductase (TryR) by recycling trypanothione disulfide (TS 2 ). (frontiersin.org)
The phenotypes of single- (SKO) and double-knockout (DKO) lines of dihydrofolate reductase-thymidylate synthase (DHFR-TS) of bloodstream Trypanosoma brucei were evaluated in vitro and in vivo. (dundee.ac.uk)
A high-throughput screening advertising campaign of a collection of 100 0 lead-like substances identified 2-iminobenzimidazoles being a book course of trypanothione reductase inhibitors. (healthandwellnesssource.org)
Some experimental as well as with tricyclic compounds has shown that they bind to the hydrophobic wall on active site formed by Trp21 and Met113 [11, 12], but in case of trypanothione reductase docking studies show that it binds to the hydrophobic region formed by Phe396, Leu399, and Pro462 [13]. (stemcellethics.net)
Trypanosoma2
Under conditions found to be the optimum for both the forward and backwards reactions, trypanothione synthase from trypanosoma cruzi was found to have an amidase activity that was only about 1% of the forwards synthetase activity. (wikipedia.org)
It was observed that induced knockout of trypanothione synthase through RNA interference caused a reduced growth rate of twofold among trypanosoma brucei due to the immediate disruption of flux through thiol redox. (wikipedia.org)
Bifunctional2
The active bifunctional enzyme of trypanothione synthase is found as a 74.4 KDa monomer consisting of 652 residues with two catalytic domains. (wikipedia.org)
T[SH] 2 is synthesized by a bifunctional trypanothione synthetase (TryS) that covalently attaches two molecules of glutathione (GSH) onto one molecule of spermidine (Spd) in a two-step process. (frontiersin.org)
Glutathione4
In enzymology, a trypanothione synthase (EC 6.3.1.9) is an enzyme that catalyzes the chemical reaction glutathione + glutathionylspermidine + ATP ⇌ {\displaystyle \rightleftharpoons } N1,N8-bis(glutathionyl)spermidine + ADP + phosphate The 3 substrates of this enzyme are glutathione, glutathionylspermidine, and ATP, whereas its 3 products are N1,N8-bis(glutathionyl)spermidine, ADP, and phosphate. (wikipedia.org)
This reaction is especially important for protozoa in the order kinetoplastida as the molecule of N1,N8-bis(glutathionyl)spermidine, also known as trypanothione, is homologous to the function of glutathione in most other prokaryotic and eukaryotic cells. (wikipedia.org)
The main function of trypanothione synthase is to use the free energy generated from ATP hydrolysis to conjugate glutathione and spermidine to form the intermediate of glutathionylspermidine and then the final product of trypanothione. (wikipedia.org)
The regulation of trypanothione synthase is currently thought to be driven by conformational changes caused by allosteric interactions as the enzyme must regulate the relative levels of spermidine, glutathionylspermidine, glutathione and trypanothione in the cell. (wikipedia.org)
Disulfide2
Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)
L'analyse d'image des cartes appariées a permis d'identifier sept protéines qui étaient soit surexprimées, soit sous-exprimées : le récepteur de la protéine kinase C activée, la tubuline alpha (×2), la prostaglandine F2-alpha synthase, la protéine disulfide isomérase, une protéine du transport vésiculaire et une protéine hypothétique. (who.int)
Activity2
In parasitic kinetoplastids trypanothione synthase activity is key to survival. (wikipedia.org)
Blunsom NJ, Gomez-Espinosa E, Ashlin TG, Cockcroft S (2018) Mitochondrial CDP-diacylglycerol synthase activity is due to the peripheral protein, TAMM41 and not due to the integral membrane protein, CDP-diacylglycerol synthase 1. (mitophysiology.org)
Form1
ADP then leaves the active site and the activated phosphate still bound to the enzyme in what is equivalent to a substituted enzyme reacts with glutathionylspermidine to form trypanothione. (wikipedia.org)
Unique1
Leishmania parasites possess an exceptional oxidant and chemical defense mechanism, involving a very unique small molecular weight thiol, trypanothione (T[SH] 2 ), that helps the parasite to manage its survival inside the host macrophage. (frontiersin.org)
Research1
The particular residues of Arg-553 and Arg-613 have been found to key for synthetic function, however further research into the structure of trypanothione synthase must be done in order to fully understand the enzyme's active sites. (wikipedia.org)
Metabolism1
Due to the need for trypanothione in order to defend against oxidative stresses, and maintain thiol and ribonucleotide metabolism. (wikipedia.org)
Protein1
Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)
Structure1
The particular residues of Arg-553 and Arg-613 have been found to key for synthetic function, however further research into the structure of trypanothione synthase must be done in order to fully understand the enzyme's active sites. (wikipedia.org)
Cell2
In other similar experiments which observed cell death after knocking out trypanothione synthase, it was shown that after two hours of being exposed to hydrogen peroxide in order to mimic the oxidant attack of phagocytes, the cells which did not contain working trypanothione synthase had a much higher death rate than wild type T. brucei. (wikipedia.org)