Expansion of the mammalian 3β‐hydroxysteroid dehydrogenase/plant dihydroflavonol reductase superfamily to include a bacterial cholesterol dehydrogenase, a bacterial UDP‐galactose‐4‐epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus

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Abstract
Mammalian 3β‐hydroxysteroid dehydrogenase and plant dihydroflavonol reductases are descended from a common ancestor. Here we present evidence that Nocardia cholesterol dehydrogenase, E. coli UDP‐galactose‐4 epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus are homologous to 3β‐hydroxysteroid dehydrogenase and dehydroflavonol reductase. Analysis of a multiple alignment of these sequences indicates that viral ORFs are most closely related to the mammalian 3β‐hydroxysteroid dehydrogenases. The ancestral protein of this superfamily is likely to be one that metabolized sugar nucleotides. The sequence similarity between 3β‐hydroxysteroid dehydrogenase and the viral ORFs is sufficient to suggest that these ORFs have an activity that is similar to 3β‐hydroxysteroid dehydrogenase or cholesterol dehydrogenase, although the putative substrates are not yet known.