Generating disulfides with the Quiescin-sulfhydryl oxidases.
The Quiescin-sulfhydryl oxidase (QSOX) family of flavoenzymes catalyzes the direct and facile insertion of disulfide bonds into unfolded reduced proteins with concomitant reduction of oxygen to hydrogen peroxide. This review discusses the chemical mechanism of these enzymes and the involvement of thioredoxin and flavin-binding domains in catalysis. The variability of CxxC motifs in the QSOX family is highlighted and attention is drawn to the steric factors that may promote efficient thiol/disulfide exchange during oxidative protein folding. The varied cellular location of these multi-domain sulfhydryl oxidases is reviewed and potential intracellular and extracellular roles are summarized. Finally, this review identifies important unresolved questions concerning this ancient family of sulfhydryl oxidases.
Heckler
Erin J
EJ
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19711, USA.
Rancy
Pumtiwitt C
PC
Kodali
Vamsi K
VK
Thorpe
Colin
C
D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors; D017510:Protein Folding; D013879:Thioredoxins / Q000502:physiology*
D004220:Disulfides; D013879:Thioredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C117183:QSOX1 protein, human