Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal.
The reduction of all-trans-retinal in photoreceptor outer segments is the first step in the regeneration of bleached visual pigments. We report here the cloning of a dehydrogenase, retSDR1, that belongs to the short-chain dehydrogenase/reductase superfamily and localizes predominantly in cone photoreceptors. retSDR1 expressed in insect cells displayed substrate specificities of the photoreceptor all-trans-retinol dehydrogenase. Homology modeling of retSDR1 using the carbonyl reductase structure as a scaffold predicted a classical Rossmann fold for the nucleotide binding, and an N-terminal extension that could facilitate binding of the enzyme to the cell membranes. The presence of retSDR1 in a subset of inner retinal neurons and in other tissues suggests that the enzyme may also be involved in retinol metabolism outside of photoreceptors.
Haeseleer
F
F
Department of Ophthalmology, University of Washington School of Medicine, Seattle, Washington 98195-6485, USA.
Huang
J
J
Lebioda
L
L
Saari
J C
JC
Palczewski
K
K
D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000201:enzymology*; D012374:Rod Cell Outer Segment / Q000201:enzymology*; D014212:Tretinoin / Q000378:metabolism*
D012333:RNA, Messenger; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C084155:alcohol dehydrogenase (NAD(P)+)