1a4u
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ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS
OverviewOverview
Drosophila alcohol dehydrogenase (DADH; EC 1.1.1.1) is a NAD(H)-dependent, oxidoreductase belonging to the short-chain dehydrogenases/reductases, (SDR) family. This homodimeric enzyme catalyzes the dehydrogenation of, alcohols to their respective ketones or aldehydes in the fruit-fly, Drosophila, both for metabolic assimilation and detoxification purposes., The crystal structure of the apo form of DADH, one of the first, biochemically characterized member of the SDR family, was solved at 1.9 A, resolution by Patterson methods. The initial model was improved by, crystallographic refinement accompanied by electron density averaging, R-factor=20.5%, R-free=23.8%.DADH subunits show an alpha/beta single, domain structure with a characteristic NAD(H) binding motif (Rossmann, fold). The peptide chain of a subunit is folded into a central, eight-stranded beta-sheet flanked on each side by three alpha-helices. The, dimers have local 2-fold symmetry. Dimer association is dominated by a, four-helix bundle motif as well as two C-terminal loops from each subunit, which represent a unique structural feature in SDR enzymes with known, structure.Three structural features are characteristic for the active site, architecture. (1) A deep cavity which is covered by a flexible loop (33, residues) and the C-terminal tail (11 residues) from the neighboring, subunit. The hydrophobic surface of the cavity is likely to increase the, specificity of this enzyme towards secondary aliphatic alcohols. (2) The, residues of the catalytic triad (Ser138, Tyr151, Lys155) are known to be, involved in enzymatic catalysis in the first line. The Tyr151 OH group is, involved in an ionic bond with the Lys155 side-chain. Preliminary, electrostatic calculations have provided evidence that the active form of, Tyr151 is a tyrosinate ion at physiological pH. (3) Three well-ordered, water molecules in hydrogen bond distance to side-chains of the catalytic, triad may be significant for the proton release steps in DADH catalysis.A, ternary structure-based sequence alignment with ten members of the SDR, family with known three-dimensional structure has suggested to define a, model consisting of four groups of residues, which relates the observed, low degree of sequence identity to quite similar folding patterns and, nearly identical distributions of residues involved in catalysis.
About this StructureAbout this Structure
1A4U is a Single protein structure of sequence from Scaptodrosophila lebanonensis. Active as Alcohol dehydrogenase, with EC number 1.1.1.1 Known structural/functional Sites: , , , and . Full crystallographic information is available from OCA.
ReferenceReference
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. 1998 Sep 18;282(2):383-99. PMID:9735295
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