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.
Department of Ophthalmology, University of Washington School of Medicine, Seattle, Washington 98195-6485, USA.
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F
Haeseleer
J
J
Huang
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L
Lebioda
J C
JC
Saari
K
K
Palczewski
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)+)