Structural Insights into the Drosophila melanogaster Retinol Dehydrogenase, a Member of the Short-Chain Dehydrogenase/Reductase Family.

The 11-cis-retinylidene chromophore of visual pigments isomerizes upon interaction with a photon, initiating a downstream cascade of signaling events that ultimately lead to visual perception. 11-cis-Retinylidene is regenerated through the enzymatic transformations collectively called visual cycle. The first and rate-limiting enzymatic reaction within this cycle, i.e. the reduction of all-trans–retinal to all-trans-retinol, is catalyzed by retinol dehydrogenases. Here, we solved the structure of Drosophila melanogaster photoreceptor retinol dehydrogenase (PDH) isoform C (PDHc) that belongs to the short-chain dehydrogenase/reductase (SDR) family. This is the first reported structure of a SDR that possesses this biologically important activity. Two crystal structures of the same enzyme grown under different conditions revealed a novel conformational change of the NAD+ co-factor, likely representing conformational changes during catalysis. Amide hydrogen–deuterium exchange of PDH demonstrates changes in the ...