Database: PROSITE(DOC)
Entry: PDOC00063
LinkDB: PDOC00063
Original site: PDOC00063 
* D-isomer specific 2-hydroxyacid dehydrogenases signatures *

A number  of  NAD-dependent 2-hydroxyacid  dehydrogenases  which  seem  to  be
specific for the D-isomer of their substrate  have  been shown [1,2,3,4] to be
functionally and structurally related. These enzymes are listed below.

 - D-lactate dehydrogenase (EC, a  bacterial  enzyme which catalyzes
   the reduction of D-lactate to pyruvate.
 - D-glycerate dehydrogenase  (EC   (NADH-dependent  hydroxypyruvate
   reductase), a plant leaf peroxisomal enzyme that catalyzes the reduction of
   hydroxypyruvate  to  glycerate.  This  reaction  is  part  of the glycolate
   pathway of photorespiration.
 - D-glycerate dehydrogenase from the bacteria Hyphomicrobium methylovorum and
   Methylobacterium extorquens.
 - 3-phosphoglycerate dehydrogenase  (EC, a  bacterial  enzyme  that
   catalyzes the oxidation of D-3-phosphoglycerate to 3-phosphohydroxypyruvate.
   This reaction  is  the first committed step in the 'phosphorylated' pathway
   of serine biosynthesis.
 - Erythronate-4-phosphate dehydrogenase (EC 1.1.1.-) (gene pdxB), a bacterial
   enzyme involved in the biosynthesis of pyridoxine (vitamin B6).
 - D-2-hydroxyisocaproate  dehydrogenase (EC 1.1.1.-) (D-hicDH),  a  bacterial
   enzyme that catalyzes  the  reversible  and stereospecific  interconversion
   between 2-ketocarboxylic acids and D-2-hydroxy-carboxylic acids.
 - Formate dehydrogenase (EC (FDH) from  the bacteria Pseudomonas sp.
   101 and various fungi [5].
 - Vancomycin  resistance protein vanH from Enterococcus faecium; this protein
   is a  D-specific alpha-keto acid dehydrogenase involved in the formation of
   a peptidoglycan  which  does  not  terminate  by  D-alanine thus preventing
   vancomycin binding.

 - Escherichia coli hypothetical protein ycdW.
 - Escherichia coli hypothetical protein yiaE.
 - Haemophilus influenzae hypothetical protein HI1556.
 - Yeast hypothetical protein YER081w.
 - Yeast hypothetical protein YIL074w.

All these enzymes  have  similar enzymatic  activities  and  are  structurally
related.  We  have  selected  three  of  the  most conserved  regions of these
proteins to develop patterns.  The  first  pattern  is based on a glycine-rich
region located in the central section of these enzymes,  this  region probably
corresponds to the NAD-binding domain. The two other patterns contain a number
of conserved charged residues,  some of which may play a role in the catalytic

-Consensus pattern: [LIVMA]-[AG]-[IVT]-[LIVMFY]-[AG]-x-G-[NHKRQGSAC]-[LIV]-G-
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for 5 sequences.
-Other sequence(s) detected in Swiss-Prot: 5.

-Consensus pattern: [LIVMFYWA]-[LIVFYWC]-x(2)-[SAC]-[DNQHR]-[IVFA]-[LIVF]-x-
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for 5 sequences.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: [LMFATCYV]-[KPQNHAR]-x-[GSTDNK]-x-[LIVMFYWRC]-
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for 2 sequences.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: Escherichia coli D-lactate  dehydrogenase (gene dld) does not belong to
 this family, it is a membrane-bound FAD flavoenzyme.

-Last update: April 2006 / Pattern revised.

[ 1] Grant G.A.
     "A new family of 2-hydroxyacid dehydrogenases."
     Biochem. Biophys. Res. Commun. 165:1371-1374(1989).
[ 2] Kochhar S., Hunziker P.E., Leong-Morgenthaler P., Hottinger H.
     "Evolutionary relationship of NAD(+)-dependent D-lactate
     dehydrogenase: comparison of primary structure of 2-hydroxy acid
     Biochem. Biophys. Res. Commun. 184:60-66(1992).
[ 3] Taguchi H., Ohta T.
     "D-lactate dehydrogenase is a member of the D-isomer-specific
     2-hydroxyacid dehydrogenase family. Cloning, sequencing, and
     expression in Escherichia coli of the D-lactate dehydrogenase gene of
     Lactobacillus plantarum."
     J. Biol. Chem. 266:12588-12594(1991).
[ 4] Goldberg J.D., Yoshida T., Brick P.
     "Crystal structure of a NAD-dependent D-glycerate dehydrogenase at 2.4
     A resolution."
     J. Mol. Biol. 236:1123-1140(1994).
[ 5] Popov V.O., Lamzin V.S.
     "NAD(+)-dependent formate dehydrogenase."
     Biochem. J. 301:625-643(1994).
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