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Publication Abstract from PubMed

Peroxiredoxin IV (PrxIV) is an endoplasmic reticulum (ER) localized enzyme that metabolizes the hydrogen peroxide produced by ER oxidase 1 (Ero1). It has been shown to play a role in de novo disulfide formation, oxidizing members of the protein disulfide isomerase (PDI) family of enzymes and is a member of the typical 2-cys peroxiredoxin family. We have determined the crystal structure of both reduced and disulfide-bonded, as well as a resolving cysteine mutant of human PrxIV. We show that PrxIV has a similar structure to other typical 2-cys peroxiredoxins and undergoes a conformational change from a fully folded (FF) to a locally unfolded (LU) form following the formation of a disulfide between the peroxidatic and resolving cysteine residues. Unlike other mammalian typical 2-cys peroxiredoxins, we show that PrxIV forms a stable decameric structure even in its disulfide bonded state. In addition, the structure of a resolving cysteine mutant reveals an intermediate in the reaction cycle that adopts the LU conformation. Interestingly the peroxidatic cysteine in the crystal structure is sulfenylated rather than sulfinylated or sulfonylated. In addition, the peroxidatic cysteine in the resolving cysteine mutant is resistant to hyper-oxidation following incubation with high concentration of hydrogen peroxide. These results highlight some unique properties of PrxIV and suggest that the equilibrium between the FF and LU forms favors the LU conformation upon sulfenylation of the peroxidatic cysteine residue.

Crystal structure of reduced and of oxidized peroxiredoxin IV reveals a stable oxidized decamer and a non disulfide-bonded intermediate in the catalytic cycle.,Cao Z, Tavender TJ, Roszak AW, Cogdell RJ, Bulleid NJ J Biol Chem. 2011 Oct 12. PMID:21994946^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.