Fig. 3

Riboflavin-responsive mutants of ETF-QO. The alignment was generated for known (or predicted) ETF-QO sequences from human (Homo sapiens AAB24227.1), pig (Sus scrofa, XP_003129051.1), mouse (Mus musculus, NP_080070.2), frog (Xenopus laevis, NP_001087869.1), zebra fish (Danio rerio, NP_001004598.1), worm (Caenorhabditis elegans, NP_001379625.1), nematode (Trichinella pseudospiralis XP_003377314.1), fruit fly (Drosophila melanogaster, NP_001246231.1), yeast (Saccharomyces cerevisiae Q08822), fungus (Absidia glauca A0A168RVN9) and bacteria (Proteobacteria, MCR9071071.1) using ClustalX [113]. Amino acid numbers for the human sequence are indicated. Red boxes indicate the locations of the human variant amino acids Gly77, Ser82, Ala84, Arg175, Ala187 and Gly191 that are associated with adult-onset riboflavin-responsive disease. The GXGXXG adenine binding motif is indicated with a black bracket. Black boxes indicate Ser115 and Ala117 that are involved in hydrogen bonding with the tricyclic isoalloxazine rings of FAD. Two different views of ribbon diagrams (generated in VMD 1.9.1) [114] of the crystal structure of porcine ETF-QO B, C [49] in complex with FAD (white) are shown. B Gly77 (yellow), Ser82 (grey) and Ala84 (orange) that are highlighted in the red boxes of panel A are subject to mutations that are associated with riboflavin responsive disease. C Arg175 (pink), Ala187 (cyan) and Gly191 (purple) that are highlighted in the red boxes of panel A are subject to mutations that are associated with riboflavin responsive diseases