Kinetic modelling of Trypanothione Synthetase to elucidate the enzyme mechanism and an overall rate equation
The enzyme Trypanothione Synthetase (TryS) is a complex enzyme that catalyses the two step reaction that forms trypanothione from 2 molecules of GSH and 1 molecule of Spd and the use of ATP
SEEK ID: https://fairdomhub.org/studies/101
Experimentalists: Jurgen Haanstra, Alejandro Leroux
Created: 6th Dec 2012 at 17:37
Last updated: 31st Jul 2014 at 10:14
The SilicoTryp project aims at the creation of a “Silicon Trypanosome”, a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology.
Trypanosomes are blood-stream parasites transmitted by tsetse flies; they cause African sleeping sickness in humans and livestock. Currently available drugs have severe side effects, and the parasites are rapidly developing resistance.
In this project, we collect a wide range of new experimental data on the parasite in its various
Aim. To provide critical quantitative parameter information and to model redox balance by determining the cellular concentration of all enzymes involved in the trypanothione-dependent hydroperoxide detoxification system of trypanosomes and by performing the kinetic characterization of the involved enzymes under pseudo-physiological conditions.
Snapshots: No snapshots
Studies: Determination of the redox state and the total concentration of the tryp..., Kinetic characterization of trypanothione-dependent enzymes, Kinetic modelling of Trypanothione Synthetase to elucidate the enzyme me...
We here create a kinetic model for a single enzyme within the T. brucei trypanothione synthesis pathway, the enzyme trypanothione synthetase based on the insights from the laboratory experiments
Investigation: Kinetic understanding of the T. brucei trypanot...
Organisms: No organisms
Models: Final model of TryS
SOPs: No SOPs
All datapoints that were measured are displayed together with the accompanying simulations by the computational model
TbTryS activity was measured at 37°C in the in vivo-like buffer. All substrate stock solutions were prepared in the in vivo-like buffer and the pH was adjusted to 7.0. The assays were performed in a final volume of 2 ml and contained 0.2 mM NADH, 1 mM phosphoenolpyruvate, 4 units pyruvate kinase, 4 units L-lactate dehydrogenase, 0.17 µM TbTryS, 2.1 mM ATP and varying amounts of GSH, and Spd.
An extended model description of the TryS model
The file contains the initial rate measurements of TbTryS obtained under different substrate and product initial concentrations.
Mechanistical model of the catalytic cycle of Trypanothione Synthetase
Contributor: Jurgen Haanstra
Model type: Linear equations
Model format: Copasi
Organism: Trypanosoma brucei
Investigations: Kinetic understanding of the T. brucei trypanot...
Modelling analyses: Creating kinetic model of Trypanothione Synthetase
Date Published: 3rd Jul 2013
Journal: J. Biol. Chem.
PubMed ID: 23814051