InterPro domain: IPR012133

This group represents an alpha-hydroxy acid dehydrogenase, which is FMN-dependent. Human glycolate oxidase (GO) catalyses the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate. The latter is a key metabolite in kidney stone formation. 4-carboxy-5-dodecylsulphanyl-1,2,3-triazole (CDST) is an inhibitor of this enzyme. In contrast to most alpha-hydroxy acid oxidases, including spinach glycolate oxidase, a loop region, known as loop 4, is completely visible when the GO active site contains a small ligand. Since this is an unique structural feature, it has the potential to be a target for drugs to decrease glycolate and glyoxylate levels in primary hyperoxaluria type 1 patients who have the inability to convert peroxisomal glyoxylate to glycine [ 1 ]. In addition, L-Lactate oxidase (LOX) belongs to a family of flavin mononucleotide (FMN)-dependent alpha-hydroxy acid-oxidizing enzymes [ 2 ]. This entry also includes the fungal protein FUB9 by virtue of sequence similarity to the FMN-dependent alpha-hydroxy acid dehydrogenase family. FUB9 is an oxidase that is part of the gene cluster that mediates the biosynthesis of fusaric acid [ 3 ].

1. Active site and loop 4 movements within human glycolate oxidase: implications for substrate specificity and drug design. Biochemistry 47, 2439-49
2. X-ray structures of Aerococcus viridans lactate oxidase and its complex with D-lactate at pH 4.5 show an alpha-hydroxyacid oxidation mechanism. J. Mol. Biol. 378, 436-46
3. Identification of a 12-gene Fusaric Acid Biosynthetic Gene Cluster in Fusarium Species Through Comparative and Functional Genomics. Mol. Plant Microbe Interact. 28, 319-32