InterPro: IPR017905 ERV/ALR sulphydryl oxidase

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, 4]. 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 [5].