PROSITE documentation PDOC00482
FMN-dependent alpha-hydroxy acid dehydrogenase signature and profile


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, 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 ((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, a peroxisomal enzyme.
  • Lactate 2-monooxygenase (EC (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 [5] 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.

Last update:

December 2007 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

FMN_HYDROXY_ACID_DH_2, PS51349; FMN-dependent alpha-hydroxy acid dehydrogenase domain profile  (MATRIX)

FMN_HYDROXY_ACID_DH_1, PS00557; FMN-dependent alpha-hydroxy acid dehydrogenases active site  (PATTERN)


1AuthorsGiegel D.A. Williams C.H. Jr. Massey V.
TitleL-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning, nucleotide sequence, and primary structure homology within an enzyme family.
SourceJ. Biol. Chem. 265:6626-6632(1990).
PubMed ID2324094

2AuthorsTsou A.Y. Ransom S.C. Gerlt J.A. Buechter D.D. Babbitt P.C. Kenyon G.L.
TitleMandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli.
SourceBiochemistry 29:9856-9862(1990).
PubMed ID2271624

3AuthorsDiep Le K.H. Lederer F.
TitleAmino 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.
SourceJ. Biol. Chem. 266:20877-20881(1991).
PubMed ID1939137

4AuthorsCunane L.M. Barton J.D. Chen Z.W. Le K.H. Amar D. Lederer F. Mathews F.S.
TitleCrystal structure analysis of recombinant rat kidney long chain hydroxy acid oxidase.
SourceBiochemistry 44:1521-1531(2005).
PubMed ID15683236

5AuthorsLindqvist Y. Branden C.-I.
TitleThe active site of spinach glycolate oxidase.
SourceJ. Biol. Chem. 264:3624-3628(1989).
PubMed ID2644287

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