Sulfhydryl oxidases: emerging catalysts of protein disulfide bond formation in eukaryotes.
Members of the Quiescin-sulfhydryl oxidase (QSOX) family utilize a thioredoxin domain and a small FAD-binding domain homologous to the yeast ERV1p protein to oxidize sulfhydryl groups to disulfides with the reduction of oxygen to hydrogen peroxide. QSOX enzymes are found in all multicellular organisms for which complete genomes exist and in Trypanosoma brucei, but are not found in yeast. The avian QSOX is the best understood enzymatically: its preferred substrates are peptides and proteins, not monothiols such as glutathione. Mixtures of avian QSOX and protein disulfide isomerase catalyze the rapid insertion of the correct disulfide pairings in reduced RNase. Immunohistochemical studies of human tissues show a marked and highly localized concentration of QSOX in cell types associated with heavy secretory loads. Consistent with this role in the formation of disulfide bonds, QSOX is typically found in the cell in the endoplasmic reticulum and Golgi and outside the cell. In sum, this review suggests that QSOX enzymes play a significant role in oxidative folding of a large variety of proteins in a wide range of multicellular organisms.
Thorpe
Colin
C
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA. cthorpe@udel.edu
Hoober
Karen L
KL
Raje
Sonali
S
Glynn
Nicole M
NM
Burnside
Joan
J
Turi
George K
GK
Coppock
Donald L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds; D004220:Disulfides; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010088:Oxidoreductases / Q000378:metabolism* / Q000502:physiology*; D010802:Phylogeny; D012503:Saponins; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000378:metabolism; D014345:Trypanosoma; D050862:Oxidoreductases Acting on Sulfur Group Donors
D004220:Disulfides; D010088:Oxidoreductases; D012503:Saponins; D013879:Thioredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C078785:saponin QA-21V1