Alcohol dehydrogenase-related
InterPro Protein Domain record
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description
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<p>The short-chain dehydrogenases/reductases family (SDR) [<cite idref="PUB00000419"/>] 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 [<cite idref="PUB00001371"/>, <cite idref="PUB00001399"/>, <cite idref="PUB00001408"/>] '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 [<cite idref="PUB00004592"/>], 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 [<cite idref="PUB00004592"/>].</p><p>Insect ADH is very different from yeast and mammalian ADHs. The enzyme from <taxon tax_id="7225">Drosophila lebanonensis</taxon> (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 [<cite idref="PUB00001371"/>]. 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 [<cite idref="PUB00014249"/>]. 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.</p> <p> 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) [<cite idref="PUB00000419"/>]; drosophila fat body protein; and development-specific 25Kd protein from <taxon tax_id="7386">Sarcophaga peregrina</taxon> (Flesh fly).</p>
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label
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Alcohol dehydrogenase-related
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signatures_SMART
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InterPro Protein Domain record
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