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PDB:1RP4

Protein Name

Flavoenzyme Ero1p

Species

Saccharomyces cerevisiae (Baker's yeast)

Biological Context

The flavoenzyme Ero1p, with a bound flavin adenine dinucleotide (FAD) cofactor, catalyzes the redox reaction of FAD by switching between the oxidation and reduction states. Ero1p generates the disulfide bonds for oxidative protein folding in the endoplasmic reticulum. These disulfide bonds are transferred to protein disulfide isomerase (PDI) and then to substrate proteins via dithiol-disulfide exchange reactions. In other words, Ero1p catalyzes the thiol oxidation of the active site in PDI, and PDI then transfers these disulfide bonds to substrate proteins. Such disulfide bond formation as a posttranslational modification step is essential for protein stabilization and redox control. However the mechanism has not yet been discovered.

Structure Description

1rp41rp4_x1rp4_y

The structure of Ero1p with a bound FAD has been determined. Ero1p contains multiple alpha-helices and two loops which approach each other in the middle to form a short beta-sheet. In addition this enzyme has five disulfide bonds. The conserved CXXCXXC motif of Ero1p consists of Cys349, Cys352 and Cys355; Cys352 and Cys355 pair to form a disulfide bond, and Cys349 pairs with Cys90. It is known that, of the five disulfide bond pairs, the Cys352/Cys355 pair is important for disulfide bond formation and the Cys100/Cys105 pair is involved in the transfer of the disulfide bonds to PDI. This crystal structure has suggested a mechanism for the disulfide transfer. The flexible loop including Cys100/Cys105 accepts the electrons from PDI, and transfers them to Cys352/Cys355 in the active site of Ero1p. An intermediate disulfide bond is then formed between Cys105 and Cys352 for the transfer of the electrons, coupled with a conformational change of the backbone of this loop.

Protein Data Bank (PDB)

References

Source

Gross, E. Kastner, D.B. Kaiser, C.A. Fass, D.; "Structure of ero1p, source of disulfide bonds for oxidative protein folding in the cell."; Cell (Cambridge,Mass.); (2004) 117:601-610 PubMed:15163408.

Others

UniProt:Q03103

author: Yuko Tsuchiya


Japanese version:PDB:1RP4