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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 1.1.2.3), 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 1.1.3.15) ((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 1.1.3.15), a peroxisomal enzyme.
• Lactate 2-monooxygenase (EC 1.13.12.4) (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.

December 2007 / Text revised; profile added.

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)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Domain architecture view of Swiss-Prot proteins matching PS51349 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51349 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51349 • Scan Swiss-Prot/TrEMBL entries against PS51349 • view ligand binding statistics

Matching PDB structures: 1AL7 1AL8 1FCB 1GOX ... [ALL]

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

Consensus pattern: S-N-H-G-[AG]-R-Q H is the active site residue; R is a substrate-binding residue Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00557 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00557 • Scan Swiss-Prot/TrEMBL entries against PS00557 • view ligand binding statistics

Matching PDB structures: 1AL7 1AL8 1FCB 1GOX ... [ALL]

1	Authors	Giegel D.A., Williams C.H. Jr., Massey V.
	Title	L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning, nucleotide sequence, and primary structure homology within an enzyme family.
	Source	J. Biol. Chem. 265:6626-6632(1990).
	PubMed ID	2324094

2	Authors	Tsou A.Y., Ransom S.C., Gerlt J.A., Buechter D.D., Babbitt P.C., Kenyon G.L.
	Title	Mandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli.
	Source	Biochemistry 29:9856-9862(1990).
	PubMed ID	2271624

3	Authors	Diep Le K.H., Lederer F.
	Title	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.
	Source	J. Biol. Chem. 266:20877-20881(1991).
	PubMed ID	1939137

4	Authors	Cunane L.M., Barton J.D., Chen Z.W., Le K.H., Amar D., Lederer F., Mathews F.S.
	Title	Crystal structure analysis of recombinant rat kidney long chain hydroxy acid oxidase.
	Source	Biochemistry 44:1521-1531(2005).
	PubMed ID	15683236
	DOI	10.1021/bi048616e

5	Authors	Lindqvist Y., Branden C.-I.
	Title	The active site of spinach glycolate oxidase.
	Source	J. Biol. Chem. 264:3624-3628(1989).
	PubMed ID	2644287

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