{PDOC00482}
{PS00557; FMN_HYDROXY_ACID_DH_1}
{PS51349; FMN_HYDROXY_ACID_DH_2}
{BEGIN}
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* FMN-dependent alpha-hydroxy acid dehydrogenase signature and profile *
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A  number  of  oxidoreductases  that  act on alpha-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 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 [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  alpha-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.

-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.

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

-Last update: December 2007 / Text revised; profile added.

[ 1] Giegel D.A., Williams C.H. Jr., Massey V.
     "L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning,
     nucleotide sequence, and primary structure homology within an enzyme
     family."
     J. Biol. Chem. 265:6626-6632(1990).
     PubMed=2324094
[ 2] Tsou A.Y., Ransom S.C., Gerlt J.A., Buechter D.D., Babbitt P.C.,
     Kenyon G.L.
     "Mandelate pathway of Pseudomonas putida: sequence relationships
     involving mandelate racemase, (S)-mandelate dehydrogenase, and
     benzoylformate decarboxylase and expression of benzoylformate
     decarboxylase in Escherichia coli."
     Biochemistry 29:9856-9862(1990).
     PubMed=2271624
[ 3] Diep Le K.H., Lederer F.
     "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."
     J. Biol. Chem. 266:20877-20881(1991).
     PubMed=1939137
[ 4] Cunane L.M., Barton J.D., Chen Z.W., Le K.H., Amar D., Lederer F.,
     Mathews F.S.
     "Crystal structure analysis of recombinant rat kidney long chain
     hydroxy acid oxidase."
     Biochemistry 44:1521-1531(2005).
     PubMed=15683236; DOI=10.1021/bi048616e
[ 5] Lindqvist Y., Branden C.-I.
     "The active site of spinach glycolate oxidase."
     J. Biol. Chem. 264:3624-3628(1989).
     PubMed=2644287

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