A number of oxidoreductases that act on α-hydroxy acids and which are
FMN-containing flavoproteins have been shown [1,2,3,4] to be structurally
related; these enzymes are:
Lactate dehydrogenase (EC 184.108.40.206), which consists of a dehydrogenase
domain and a heme-binding domain called cytochrome b2 and which catalyzes
the conversion of lactate into pyruvate.
Glycolate oxidase (EC 220.127.116.11) ((S)-2-hydroxy-acid oxidase), a peroxisomal
enzyme that catalyzes the conversion of glycolate and oxygen to glyoxylate
and hydrogen peroxide.
Long chain α-hydroxy acid oxidase from rat (EC 18.104.22.168), a peroxisomal
Lactate 2-monooxygenase (EC 22.214.171.124) (lactate oxidase) from Mycobacterium
smegmatis, which catalyzes the conversion of lactate and oxygen to acetate,
carbon dioxide and water.
(S)-mandelate dehydrogenase from Pseudomonas putida (gene mdlB), which
catalyzes 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 α-carbon of the substrate producing a carbanion
which can subsequently attach to the N5 atom of FMN. A conserved histidine has
been shown  to be involved in the removal of the proton. We selected for a
signature pattern the region around this active site residue, which is highly
conserved and contains an arginine residue which is involved in substrate
binding. Three-dimensional structures of FMN-dependent α-hydroxy acid
dehydrogenases show a common fold with a TIM barrel structure (see
<PDB:1TB3>). We also developed a profile that covers the entire FMN hydroxy
acid dehydrogenase domain.
Mandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli.
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