Drosophila alcohol dehydrogenase: evaluation of Ser139 site-directed mutants

Abstract
Drosophila alcohol dehydrogenase (DADH) belongs to the large and highly heterogeneous (15–30% residue identity) short‐chain dehydrogenase/reductase family (SDR). It is the only reported member that oxidizes mainly ethanol and 2‐propanol among other alcohols. To confirm the role of Ser139 we constructed two site‐directed mutants, Ser139Ala and Ser139Cys, which show no enzymatic activity. Molecular replacement and data from crystallographically refined 3D structures confirm the position of Ser139, whose hydroxyl group faces the cleft of the presumed catalytic pocket, very close to Tyr152 and Lys156. Thus, consistent with the constitution of the catalytic triad of other SDR, our results suggest that Ser139 of DADH is directly involved in the catalytic reaction.

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