PROSITE documentation PDOC00063 [for PROSITE entry PS00670]
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 α-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 mechanism.


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.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

D_2_HYDROXYACID_DH_2, PS00670; D-isomer specific 2-hydroxyacid dehydrogenases signature 2  (PATTERN)

D_2_HYDROXYACID_DH_1, PS00065; D-isomer specific 2-hydroxyacid dehydrogenases NAD-binding signature  (PATTERN)

D_2_HYDROXYACID_DH_3, PS00671; D-isomer specific 2-hydroxyacid dehydrogenases signature 3  (PATTERN)


1AuthorsGrant G.A.
TitleA new family of 2-hydroxyacid dehydrogenases.
SourceBiochem. Biophys. Res. Commun. 165:1371-1374(1989).
PubMed ID2692566

2AuthorsKochhar S. Hunziker P.E. Leong-Morgenthaler P. Hottinger H.
TitleEvolutionary relationship of NAD(+)-dependent D-lactate dehydrogenase: comparison of primary structure of 2-hydroxy acid dehydrogenases.
SourceBiochem. Biophys. Res. Commun. 184:60-66(1992).
PubMed ID1567457

3AuthorsTaguchi H. Ohta T.
TitleD-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.
SourceJ. Biol. Chem. 266:12588-12594(1991).
PubMed ID1840590

4AuthorsGoldberg J.D. Yoshida T. Brick P.
TitleCrystal structure of a NAD-dependent D-glycerate dehydrogenase at 2.4 A resolution.
SourceJ. Mol. Biol. 236:1123-1140(1994).
PubMed ID8120891

5AuthorsPopov V.O. Lamzin V.S.
TitleNAD(+)-dependent formate dehydrogenase.
SourceBiochem. J. 301:625-643(1994).
PubMed ID8053888

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