Genesis of Drosophila ADH: the shaping of the enzymatic activity from a SDR ancestor

Drosophila alcohol dehydrogenase (ADH) is an NAD(H)-dependent oxidoreductas e that catalyzes the oxidation of alcohols and aldehydes. Structurally and biochemically distinct from all the reported ADHs (typically, the mammalian medium-chain dehydrogenase/reductase-ethanol-metabolizing enzyme), it stan ds as the only small-alcohol transforming system that has originated from a short-chain dehydrogenase/reductase (SDR) ancestor. The crystal structures of the ape, binary (E(.)NAD(+)) and three ternary (E(.)NAD(+).acetone, E.N AD(+) .3-pentanone and E.NAD(+).cyclohexanone) forms of Drosophila lebanone nsis ADH have allowed us to infer the structural and kinetic features accou nting for the generation of the ADH activity within the SDR lineage. (C) 20 01 Elsevier Science Ireland Ltd. All rights reserved.