PR01169

CERATITISADH

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameCERATITISADH

Description
Imported from IPR002426

The short-chain dehydrogenases/reductases family (SDR)
[1]
is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterised was Drosophila alcohol dehydrogenase, this family used to be called
[2, 3, 4]
'insect-type', or 'short-chain' alcohol dehydrogenases. Most members of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least two domains
[5]
, the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains
[5]
.

Insect ADH is very different from yeast and mammalian ADHs. The enzyme from Drosophila lebanonensis (Fruit fly) has been characterised by protein analysis and was found to have a 254-residue protein chain with an acetyl-blocked N-terminal Met
[2]
. Comparisons with the enzyme from other species reveals that they have diverged considerably. The structural variation within Drosophila is about as large as that for mammalian zinc-containing alcohol dehydrogenase. The crystal structure of the apo form of D. lebanonensis ADH has been solved to 1.9A resolution. Three structural features characterise the active site architecture: (i) a deep cavity, covered by a flexible 33-residue loop and an 11-residue C-terminal tail of the neighbouring subunit, whose hydrophobic surface is likely to increase the specificity of the enzyme for secondary aliphatic alcohols; (ii) the Ser-Tyr-Lys residues of the catalytic triad are known to be involved in enzymatic catalysis; and (iii) three well-ordered water molecules in hydrogen bonding distance of side-chains of the catalytic triad may be significant for the proton release steps in the catalysis.

A number of proteins within the SDR family share a strong phylogenetic relationship with insect ADH. Amongst these are Drosophila ADH-related protein (duplicate of Adh or Adh-dup)
[1]
; Drosophila fat body protein; and development-specific 25Kd protein from Sarcophaga peregrina (Flesh fly). This group specifically identifies proteins related to Ceratitis capitata (Mediterranean fruit fly).

References
Imported from IPR002426

1.Short-chain dehydrogenases/reductases (SDR). Jornvall H, Persson B, Krook M, Atrian S, Gonzalez-Duarte R, Jeffery J, Ghosh D. Biochemistry 34, 6003-13, (1995). View articlePMID: 7742302

2.The primary structure of alcohol dehydrogenase from Drosophila lebanonensis. Extensive variation within insect 'short-chain' alcohol dehydrogenase lacking zinc. Villarroya A, Juan E, Egestad B, Jornvall H. Eur. J. Biochem. 180, 191-7, (1989). View articlePMID: 2707261

3.Characteristics of short-chain alcohol dehydrogenases and related enzymes. Persson B, Krook M, Jornvall H. Eur. J. Biochem. 200, 537-43, (1991). View articlePMID: 1889416

4.cis-diol dehydrogenases encoded by the TOL pWW0 plasmid xylL gene and the Acinetobacter calcoaceticus chromosomal benD gene are members of the short-chain alcohol dehydrogenase superfamily. Neidle E, Hartnett C, Ornston LN, Bairoch A, Rekik M, Harayama S. Eur. J. Biochem. 204, 113-20, (1992). View articlePMID: 1740120

5.Alcohol dehydrogenase gene of Drosophila melanogaster: relationship of intervening sequences to functional domains in the protein. Benyajati C, Place AR, Powers DA, Sofer W. Proc. Natl. Acad. Sci. U.S.A. 78, 2717-21, (1981). View articlePMID: 6789320

Supplementary References

1. The refined crystal structure of Drosophila lebanonensis alcohol dehydrogenase at 1.9 A resolution. Benach J, Atrian S, Gonzalez-Duarte R, Ladenstein R. J. Mol. Biol. 282, 383-99, (1998). View articlePMID: 9735295

2. Drosophila fat body protein P6 and alcohol dehydrogenase are derived from a common ancestral protein. Rat L, Veuille M, Lepesant JA. J. Mol. Evol. 33, 194-203, (1991). View articlePMID: 1920455

3. Purification and cDNA cloning of the alcohol dehydrogenase of the flesh fly Sarcophaga peregrina. A structural relationship between alcohol dehydrogenase and a 25-kDa protein. Horio T, Kubo T, Natori S. Eur. J. Biochem. 237, 698-703, (1996). View articlePMID: 8647115

4. Adh and Adh-dup sequences of Drosophila lebanonensis and D. immigrans: interspecies comparisons. Albalat R, Gonzalez-Duarte R. Gene 126, 171-8, (1993). View articlePMID: 8482531

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