InterPro: IPR000262 FMN-dependent dehydrogenase

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 (EC: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 (EC: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 (EC:1.1.3.15), a peroxisomal enzyme.
• Lactate 2-monooxygenase (EC: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.