Dissecting the Catalytic Mechanism of Trypanosoma brucei Trypanothione Synthetase by Kinetic Analysis and Computational Modeling
نویسندگان
چکیده
منابع مشابه
Discovery of Inhibitors of Trypanosoma Brucei Trypanothione Synthetase
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK Running title: Chemical Validation of Trypanothione Synthetase Address correspondence to: Julie A. Frearson, College of Life Sciences, James Black Centre, University of Dundee, Dow Street, Dundee, DD1 5EH. Tel: +44 1382 386247; Fax: +44 1382 386373; E-mail: j.a.frea...
متن کاملDissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods
The bifunctional trypanothione synthetase-amidase (TRYS) comprises two structurally distinct catalytic domains for synthesis and hydrolysis of trypanothione (N(1),N(8)-bis(glutathionyl)spermidine). This unique dithiol plays a pivotal role in thiol-redox homeostasis and in defence against chemical and oxidative stress in trypanosomatids. A tetracycline-dependent conditional double knockout of TR...
متن کاملTrypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase.
Trypanosoma brucei, the causative agent of African sleeping sickness, synthesizes deoxyribonucleotides via a classical eukaryotic class I ribonucleotide reductase. The unique thiol metabolism of trypanosomatids in which the nearly ubiquitous glutathione reductase is replaced by a trypanothione reductase prompted us to study the nature of thiols providing reducing equivalents for the parasite sy...
متن کاملDesign, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors
Trypanothione synthetase (TryS) is essential for the survival of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis. It is one of only a handful of chemically validated targets for T. brucei in vivo. To identify novel inhibitors of TbTryS we screened our in-house diverse compound library that contains 62,000 compounds. This resulted in the identification of si...
متن کاملSystems biology approaches to the computational modelling of trypanothione metabolism in Trypanosoma brucei
This work presents an advanced modelling procedure, which applies both structural modelling and kinetic modelling approaches to the trypanothione metabolic network in the bloodstream form of Trypanosoma brucei, the parasite responsible for African Sleeping sickness. Trypanothione has previously been identified as an essential compound for parasitic protozoa, however the underlying metabolic pro...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2013
ISSN: 0021-9258
DOI: 10.1074/jbc.m113.483289