To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC00482

FMN-dependent alpha-hydroxy acid dehydrogenase signature and profile





Description

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.

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)


References

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
DOI10.1021/bi048616e

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



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)