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Classification of alcohol and polyol dehydrogenases
This classification of alcohol (polyol) dehydrogenases is based on the primary sequences and is only valid for polyol dehydrogenases and should be modified in future, because some members of families are not fitted to the description.

  1. Medium-chain dehydrogenases/reductases (MDR)

    These dehydrogenases can be divided on the basis of Zn2+ dependence.
    On the basis of Zn2+ dependence:

    • Zinc-containing MDR

      • Polyol dehydrogenases (PHD)
      • Alcohol dehydrogenase (ADH)
      • Cinnamyl alcohol dehydrogenase (CAD)
      • Yeast alcohol dehydrogenase (YADH)

    • non-Zinc-containing MDR

      • Leukotriene B4 dehydrogenase (LTD)
      • Mitochondrial response protein (MRF)
      • Quinone oxidoreductases (QOR)
      • Acyl-CoA reductase (ACR)

  2. Short-chain dehydrogenases/reductases (SDR)

    Short-chain dehydrogenases/reductases are enzymes of about 250 amino acid residue subunits catalysing NAD or NAD dependent oxidation/reductation. Nowadays, the main feature used in the dehydrogenase classification is the presence of specific sequence motifs rather than length of polypeptide chain.

    Structurally, short-chain dehydrogenases consist from two domains, N-terminal region, responsible for coenzyme binding; usually resemble Rossmann-fold and C-terminal region, responsible for substrate binding. The structure of the substrate binding domain is very different across the family and related with the substrate structure.

    The classification of the subfamilies within Classical and Extended families is based on the sequence of the βαβ-fold, part of the Rossmann fold of the N-terminal region, involved into nucleotide binding. The numbering is given on the basis of the structure of 3α,20β-hydroxysteroid dehydrogenase (2HSD.PDB) and UDP-galactose-4-epimerase (1EK6.PDB) for Classical and Extended families, respectively.

    • Divergent polyol dehydrogenase familly


      The specific sequence is :
      Gx3SIx3[ILV]Ax6GAx[ILV]
      [DN]Vx20Dx3Hx23ISx[FY]S
      [FY]x7PxYNxMx2AK[AS]xL[DE]x3[KR][FY]xAx8RxNx2[AS][SA]GP[ILV]x[TS]x42[GA]x[ST]G

    • Classical polyol dehydrogenase familly


      Usually, these enzymes are about 250 amino acid residues length. The specific sequence is :
      [ILV]TGx3[AG][FILV]Gx3[AS]x2[FILMV]x3Gx2[ILMV]
      [DN]x18Gx[ILV][DEN]x[ILMV][ILMV][CNS][CNV][AV][AG]x21Nx2[GS]
      Gx[ILMV]xN[ILMV]x[AST]x2[AGS]x9Yx3Kx9[FILMV]x2[DE]x4G[ILV][KR][ILV][NS]x3PGx2[ST]
        The numbering is given on the basis of the structure of 3α,20β-hydroxysteroid dehydrogenase (2HSD.PDB)
        Residue: 15 36 37 38
      • cD1d
          x D x x
      • cD1e
          x E x x
      • cD2
          x x D/E x
      • cD3
          x x x D/E
      • cP1
          K/R x x x
      • cP2
          x x K/R x
      • cP3
          K/R x K/R x

    • Intermediate polyol dehydrogenase familly


      The specific sequence is :
      [FV]Vx3GxIx2[DE]x2[KR]
      [FY][WY]x[FY]D[ILV]Tx18IDxL[ILV]NGA[GT][IL]xD[DE]x13Tx3Nx2Gx2NT
      Gx3N[ILV]xSVx11Yx3Kx5F[ST]xSx8G[ILV]

    • Extended polyol dehydrogenase familly


      Usually, these enzymes are around 350 amino acid residues length. The specific sequence is :
      [ILV][ILV][ST]Gx2G[FMQY][DILV]Gx6[FILMV][ILMV]x2Gx2[ILV]
      [AG][DN][ILMV]x[DEN]x20[ILMV][FILMVY][HN]x[AG][AGST]x3[FILMV]x6Px10[DN]x2G[ST]x2[ILMV][ILMV][DEKQ]
      S[AST]x3[FHY][AGS]x7[DNS]PYx2[AST]Kx3[DE]x25G
        The numbering is given on the basis of the structure of UDP-galactose-4-epimerase (1EK6.PDB)
        Residue: 33 34 35
      • eD1
          D/E x x
      • eD2
          x x D/E
      • eD3
          x K/R x

    • Complex polyol dehydrogenase familly


      The specific sequence is :
      [ILV][ILV]TGGxGx2Gx3Ax6Gx2[ILV][ILV][ILV]x[SR]R
      [DN][ILV]x8[ILV][ILV]x11[AG][ILV]x[HN]xA[AG]x21K[ILV]xGx3[ILV]
      F[ILV]xF[AS]Sx5Gx2GQx2Yx3N[AS]x[ILMV][DEN]

  3. Iron-containing dehydrogenases

    This family of dehydrogenases is the least well characterised and not many structural dates are available. The first solved 3D structure belonging to this family is Glycerol dehydrogenase from Bacillus stearothermophilus (glycerol:NAD+ 2-oxidoreductase, EC 1.1.1.6). This family of dehydrogenases includes polyol dehydrogenases from bacteria and yeasts. Despite the name of this family, some members of this family clearly show dependence on Zn2+ rather than Fe2+ for activity. On this basis, it is possible to propose, that the name of this family will be changed. Another offered name is Family III metal-dependent polyol dehydrogenases.
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