InterPro domain: IPR000262

A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown [ 1 , 2 , 3 ] to be structurally related. These enzymes are:

• Lactate dehydrogenase ( 1.1.2.3 ), which consists of a dehydrogenase domain and a haem-binding domain called cytochrome b2 and which catalyses the conversion of lactate into pyruvate.
• Glycolate oxidase ( 1.1.3.15 ) ((S)-2-hydroxy-acid oxidase), a peroxisomal enzyme that catalyses the conversion of glycolate and oxygen to glyoxylate and hydrogen peroxide.
• Long chain alpha-hydroxy acid oxidase from rat ( 1.1.3.15 ), a peroxisomal enzyme.
• Lactate 2-monooxygenase ( 1.13.12.4 ) (lactate oxidase) from Mycobacterium smegmatis, which catalyses the conversion of lactate and oxygen to acetate, carbon dioxide and water.
• (S)-mandelate dehydrogenase from Pseudomonas putida (gene mdlB), which catalyses the reduction of (S)-mandelate to benzoylformate.

The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the alpha-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown [ 4 ] to be involved in the removal of the proton. The region around this active site residue is highly conserved and contains an arginine residue which is involved in substrate binding.

1. L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning, nucleotide sequence, and primary structure homology within an enzyme family. J. Biol. Chem. 265, 6626-32
2. Mandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli. Biochemistry 29, 9856-62
3. Amino acid sequence of long chain alpha-hydroxy acid oxidase from rat kidney, a member of the family of FMN-dependent alpha-hydroxy acid-oxidizing enzymes. J. Biol. Chem. 266, 20877-81
4. The active site of spinach glycolate oxidase. J. Biol. Chem. 264, 3624-8