Conservation profiles of QSOX sequences. The oxidoreductase module is on a pale yellow background, and the sulfhydryl oxidase module is on a green background. (A) QSOX sequence logo. Highly conserved regions discussed in the text are highlighted and numbered. (B) Conservation profile displayed on the QSOX structure. The hybrid human QSOX1 structure was generated as described in the Methods. Conserved residues are in magenta, and variable residues are in cyan, as depicted in the color scheme at the bottom right. Cysteine residues are indicated in space-filling representation, and the Trx- and Erv-CXXC motifs are labeled. The interdomain linker, missing from the structure, is depicted with dashed lines between its endpoints (cyan disks) in the two modules. The backstop is marked by a green circle. (C) Structural details of two loops in conserved regions #3 and #6. Together these loops constitute the conserved backstop in the ψErv/Erv domains against which the Trx1 domain docks. The color scheme used to indicate the level of conservation is the same as in panel B. The FAD is depicted in orange and the disulfides in yellow. Potential hydrogen bonds or salt bridges are indicated by dashed lines. Amino acid residue numbering is according to the H. sapiens QSOX1 sequence.