Structural highlights
Function
[ERO1_YEAST] Essential oxidoreductase that oxidizes proteins in the endoplasmic reticulum to produce disulfide bonds. Acts by oxidizing directly PDI1 isomerase through a direct disulfide exchange. Does not act as a direct oxidant of folding substrate, but relies on PDI1 to transfer oxidizing equivalent. Also able to oxidize directly the PDI related protein MPD2. Does not oxidize all PDI related proteins, suggesting that it can discriminate between PDI1 and related proteins. Reoxidation of ERO1 probably involves electron transfer to molecular oxygen via FAD. Acts independently of glutathione. May be responsible for a significant proportion of reactive oxygen species (ROS) in the cell, thereby being a source of oxidative stress.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The flavoenzyme Ero1p produces disulfide bonds for oxidative protein folding in the endoplasmic reticulum. Disulfides generated de novo within Ero1p are transferred to protein disulfide isomerase and then to substrate proteins by dithiol-disulfide exchange reactions. Despite this key role of Ero1p, little is known about the mechanism by which this enzyme catalyzes thiol oxidation. Here, we present the X-ray crystallographic structure of Ero1p, which reveals the molecular details of the catalytic center, the role of a CXXCXXC motif, and the spatial relationship between functionally significant cysteines and the bound cofactor. Remarkably, the Ero1p active site closely resembles that of the versatile thiol oxidase module of Erv2p, a protein with no sequence homology to Ero1p. Furthermore, both Ero1p and Erv2p display essential dicysteine motifs on mobile polypeptide segments, suggesting that shuttling electrons to a rigid active site using a flexible strand is a fundamental feature of disulfide-generating flavoenzymes.
Structure of Ero1p, source of disulfide bonds for oxidative protein folding in the cell.,Gross E, Kastner DB, Kaiser CA, Fass D Cell. 2004 May 28;117(5):601-10. PMID:15163408[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Frand AR, Kaiser CA. The ERO1 gene of yeast is required for oxidation of protein dithiols in the endoplasmic reticulum. Mol Cell. 1998 Jan;1(2):161-70. PMID:9659913
- ↑ Pollard MG, Travers KJ, Weissman JS. Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum. Mol Cell. 1998 Jan;1(2):171-82. PMID:9659914
- ↑ Frand AR, Kaiser CA. Ero1p oxidizes protein disulfide isomerase in a pathway for disulfide bond formation in the endoplasmic reticulum. Mol Cell. 1999 Oct;4(4):469-77. PMID:10549279
- ↑ Tu BP, Ho-Schleyer SC, Travers KJ, Weissman JS. Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science. 2000 Nov 24;290(5496):1571-4. PMID:11090354
- ↑ Tu BP, Weissman JS. The FAD- and O(2)-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum. Mol Cell. 2002 Nov;10(5):983-94. PMID:12453408
- ↑ Gross E, Kastner DB, Kaiser CA, Fass D. Structure of Ero1p, source of disulfide bonds for oxidative protein folding in the cell. Cell. 2004 May 28;117(5):601-10. PMID:15163408
