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Title: Mercaptopyruvate sulfurtransferase and cysteine biosynthetic pathways in Leishmania
Author: Williams, Roderick Adeyinka Malcolm
ISNI:       0000 0001 3569 4370
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2003
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Coping with oxidative stress is vital for survival of the intracellular parasite Leishmania, but the complex biochemical mechanisms involved are not fully understood. This study focused on enzymes of cysteine metabolism in Leishmania and the parts they play. Mercaptopyruvate sulfurtransferase (EC of Leishmania major and L. mexicana and serine acetyltransferase (EC, cysteine synthase (EC and cystathionine b-synthase (EC of Leishmania major have been cloned, expressed as active enzymes in Escherichia coli, and characterised. The leishmanial mercaptopyruvate sulfurtransferase is structurally peculiar in possessing a C-terminal domain of some 70 amino acids. Homologous genes of T. cruzi and T. brucei encode enzymes with a similar C-terminal domain, which suggests that the feature, not known in any other sulfurtranferase, is a characteristic of trypanosomatid parasites. Short truncations of the C-terminal domain resulted in misfolded, inactive proteins, demonstrating that the domain plays some key role in facilitating correct folding of the enzymes. The recombinant sulfurtransferase exhibit high activity towards 3-mercaptopyruvate and catalyse the transfer of sulfane to cyanide to form thiocyanate and sulfide. The sulfide can react with O-acetyl serine to yield cysteine through the action of cysteine synthase. They also use thiosulfate as a substrate and mercaptoethanol, glutathione, cysteine or reduced thioredoxin as the accepting nucleophile, the latter being oxidised. Mercaptopyruvate sulfurtransferase and cysteine synthase are expressed in all life cycle stages of Leishmania and the expression levels are increased under hypo-sulfur stress. The expression level of mercaptopyruvate sulfurtransferase is also increased under oxidative stress whereas overexpression of serine acetyltransferase, cysteine synthase and cystathionine beta-synthase in Leishmania promastigotes produced cell lines resistant to the oxidants hydrogen peroxide (0.5 mM), tert-butyl hydroperoxide (10 mM) and cumene hydroperoxide (10 mM).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology