The diversity and evolution of thioredoxin reductase: new perspectives.
The thioredoxin system is a major line of cellular defence against oxygen damage. Two distinct thioredoxin reductases found in eukaryotes have different catalytic mechanisms and a mutually exclusive distribution reflecting a complex evolutionary history. Most eukaryotes, including several important parasites, contain a low molecular weight thioredoxin reductase, apparently of bacterial origin. By contrast, animals and apicomplexan protozoa, including Plasmodium, appear to have lost this enzyme. Instead, they contain a high molecular weight thioredoxin reductase, which shares common ancestry with glutathione reductase. This article reviews these fundamental differences between the thioredoxin reductases of some parasites and their hosts, discusses their phylogenetic relationships and considers the potential of the enzymes as therapeutic targets.
Hirt
Robert P
RP
Dept of Zoology, Natural History Museum, Cromwell Rd, London, UK SW7 5BD. rch@nhm.ac.uk
Müller
Sylke
S
Embley
T Martin
TM
Coombs
Graham H
GH
D020816:Amino Acid Motifs; D000818:Animals; D019143:Evolution, Molecular; D005980:Glutathione Reductase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010271:Parasites / Q000201:enzymology* / Q000235:genetics; D010802:Phylogeny; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase