Sulfiredoxin, the cysteine sulfinic acid reductase specific to 2-Cys peroxiredoxin: its discovery, mechanism of action, and biological significance.
Peroxiredoxin (Prx) is a family of bifunctional proteins that exhibit peroxidase and chaperone activities. Prx proteins contain a conserved Cys residue that undergoes a redox change between thiol and disulfide states. 2-Cys Prx enzymes, a subgroup of Prx family, are intrinsically susceptible to reversible hyperoxidation to cysteine sulfinic acid during catalysis. Cysteine hyperoxidation of Prx was shown to result in loss of peroxidase activity and a concomitant gain of chaperone activity. Reduction of sulfinic Prx enzymes, the first known biological example of such a reaction, is catalyzed by sulfiredoxin (Srx) in the presence of ATP. Srx appears to exist solely to support the reversible sulfinic modification of 2-Cys Prx enzymes. Srx specifically binds to 2-Cys Prx enzymes by recognizing several critical surface-exposed residues of the Prxs, and transfer the gamma-phosphate of ATP to their sulfinic moiety, using its conserved cysteine as the phosphate carrier. The resulting sulfinic phosphoryl ester is reduced to cysteine after oxidation of four thiol equivalents.
Rhee
S G
SG
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea. rheesg@ewha.ac.kr
Jeong
W
W
Chang
T-S
TS
Woo
H A
HA
D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000502:physiology*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010544:Peroxidases / Q000502:physiology*; D054464:Peroxiredoxins
D018832:Molecular Chaperones; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D010544:Peroxidases; C504194:2-cys peroxiredoxin, human; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C504024:SRXN1 protein, human; D003545:Cysteine; C013461:cysteine sulfinic acid