InterPro domain: IPR036774

The ~100-residue ERV/ALR sulphydryl oxidase domain is a versatile module adapted for catalysis of disulphide bond formation in various organelles and biological settings. The ERV/ALR sulphydryl oxidase domain has a Cys-X-X-Cys dithiol/disulphide motif adjacent to a bound FAD cofactor, enabling transfer of electrons from thiol substrates to non-thiol electron acceptors. ERV/ALR family members differ in their N- or C-terminal extensions, which typically contain at least one additional disulphide bond, the hypothesised 'shuttle' disulphide. In yeast ERV1, a mitochondrial enzyme, the shuttle disulphide is N-terminal to the catalytic core; in yeast ERV2, present in the endoplasmic reticulum, it is C-terminal. The N- and C-terminal extensions can be entire domains, such as the thioredoxin-like domains ( PDOC00172 ) or short segments that do not seem to be distinct domains. Proteins of the ERV/ALR family are encoded by all eukaryotes and cytoplasmic DNA viruses (poxviruses, African swine fever virus, iridoviruses, and Paramecium bursaria Chlorella virus 1) [ 1 , 2 , 3 , 4 , 5 ].

The ERV/ALR sulphydryl oxidase domain contains a four-helix bundle (helices alpha1-alpha4) and an additional single turn of helix (alpha5) packed perpendicular to the bundle [ 6 , 7 ]. The FAD prosthetic group is housed at the mouth of the 4-helix bundle and communicates with the pair of juxtaposed cysteine residues that form the proximal redox active site [ 7 ].

1. Homology between egg white sulfhydryl oxidase and quiescin Q6 defines a new class of flavin-linked sulfhydryl oxidases. J. Biol. Chem. 274, 31759-62
2. A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation. Proc. Natl. Acad. Sci. U.S.A. 97, 12068-73
3. A new FAD-binding fold and intersubunit disulfide shuttle in the thiol oxidase Erv2p. Nat. Struct. Biol. 9, 61-7
4. Gain of function in an ERV/ALR sulfhydryl oxidase by molecular engineering of the shuttle disulfide. J. Mol. Biol. 362, 89-101
5. Erv2p: characterization of the redox behavior of a yeast sulfhydryl oxidase. Biochemistry 46, 3246-54
6. [New method for the exact determination of changes in the size of the leg for the quantification of therapeutic success in various angiopathies] null 25, 438-9