Similarities and differences in the thioredoxin superfamily.
There is growing interest in the proteins involved in protein folding. This is mainly due to the large number of human diseases related to defects in folding, which include cystic fibrosis, Alzheimer's and cancer. However, equally important as the oxidation and concomitant formation of disulfide bridges of the extracellular or secretory proteins is the reduction and maintenance in the reduced state of the proteins within the cell. Interestingly, the proteins that are responsible for maintenance of the reduced state belong to the same superfamily as those responsible for the formation of disulfide bridges: all are members of the thioredoxin superfamily. In this article, we highlight the main features of those thioredoxin-like proteins directly involved in the redox reactions. We describe their biological functions, cytoplasmic location, mechanisms of action, structures and active site features, and discuss the principal hypotheses concerning origins of the different reduction potentials and unusual pK(a)'s of the catalytic residues.
Carvalho
Alexandra P
AP
Requimte, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Portugal. acarvalho@fc.up.pt
Fernandes
Pedro A
PA
Ramos
Maria J
MJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D004220:Disulfides; D029968:Escherichia coli Proteins; D013879:Thioredoxins; D019704:Protein Disulfide-Isomerases