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.
Trypanothione reductase belongs to the family of flavoprotein disulphide oxidoreductases that include glutathione reductases, dihydrolipoamide dehydrogenases and mercuric reductases. Trypanothione reductase and its substrate, trypanothione disulphide, are unique to parasitic trypanosomatids responsible for several tropical diseases. The crystal structure of the enzyme from Crithidia fasciculata is currently under investigation as an aid in the design of selective inhibitors with a view to producing new drugs. We report here the cloning and sequencing of the genes for trypanothione reductase from C. fasciculata and Trypanosoma brucei. Alignment of the deduced amino acid sequences with 21 other members of this family provides insight into the role of certain amino acid residues with respect to substrate specificity and catalytic mechanism as well as conservation of certain elements of secondary structure.
Aboagye-Kwarteng
T
T
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.
Smith
K
K
Fairlamb
A H
AH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D016831:Crithidia fasciculata / Q000201:enzymology* / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics*; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics
D016054:DNA, Protozoan; D005420:Flavoproteins; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D008058:Dihydrolipoamide Dehydrogenase; D005980:Glutathione Reductase; D006867:Hydrolases