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| PROSITE documentation PDOC00482 [for PROSITE entry PS51349] |
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 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.
Last update:December 2007 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
| 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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