A new FAD-binding fold and intersubunit disulfide shuttle in the thiol oxidase Erv2p.
Erv2p is an FAD-dependent sulfhydryl oxidase that can promote disulfide bond formation during protein biosynthesis in the yeast endoplasmic reticulum. The structure of Erv2p, determined by X-ray crystallography to 1.5 A resolution, reveals a helix-rich dimer with no global resemblance to other known FAD-binding proteins or thiol oxidoreductases. Two pairs of cysteine residues are required for Erv2p activity. The first (Cys-Gly-Glu-Cys) is adjacent to the isoalloxazine ring of the FAD. The second (Cys-Gly-Cys) is part of a flexible C-terminal segment that can swing into the vicinity of the first cysteine pair in the opposite subunit of the dimer and may shuttle electrons between substrate protein dithiols and the FAD-proximal disulfide.
Gross
Einav
E
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Sevier
Carolyn S
CS
Vala
Andrea
A
Kaiser
Chris A
CA
Fass
Deborah
D
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D004579:Electron Transport; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D018583:Pliability; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D004220:Disulfides; D005656:Fungal Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D005182:Flavin-Adenine Dinucleotide; D010088:Oxidoreductases; C111280:ERV2 protein, S cerevisiae; D003545:Cysteine; D010100:Oxygen