PS00557

FMN-dependent alpha-hydroxy acid dehydrogenases active site

PROSITE patterns entry
Member databasePROSITE patterns
PROSITE patterns typeconserved site
Short nameFMN_HYDROXY_ACID_DH_1

Description

A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown
[4]
[3]
[5]
[1]
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 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 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 alpha-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown
[2]
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 alpha-hydroxy acid dehydrogenases show a common fold with a TIM barrel structure. We also developed a profile that covers the entire FMN hydroxy acid dehydrogenase domain.

References

1.Crystal structure analysis of recombinant rat kidney long chain hydroxy acid oxidase. Cunane LM, Barton JD, Chen ZW, Le KH, Amar D, Lederer F, Mathews FS. Biochemistry 44, 1521-31, (2005). View articlePMID: 15683236

2.The active site of spinach glycolate oxidase. Lindqvist Y, Branden CI. J. Biol. Chem. 264, 3624-8, (1989). View articlePMID: 2644287

3.Mandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli. Tsou AY, Ransom SC, Gerlt JA, Buechter DD, Babbitt PC, Kenyon GL. Biochemistry 29, 9856-62, (1990). View articlePMID: 2271624

4.L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning, nucleotide sequence, and primary structure homology within an enzyme family. Giegel DA, Williams CH Jr, Massey V. J. Biol. Chem. 265, 6626-32, (1990). View articlePMID: 2324094

5.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. Diep Le KH, Lederer F. J. Biol. Chem. 266, 20877-81, (1991). View articlePMID: 1939137

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