The short-chain alcohol dehydrogenase superfamily: variations on a common theme.
Multiple alignment of members of the short-chain alcohol dehydrogenase (SCAD) superfamily, according to the conserved domains A-F, has revealed a number of important relationships. It can be shown that the 17 beta-hydroxysteroid dehydrogenase type 2 enzyme is more closely related to D-beta-hydroxybutyrate dehydrogenase than it is to 17 beta-hydroxysteroid dehydrogenase type 1. Carbonyl reductase, previously considered to be a member of the aldo-keto reductase superfamily, displayed high homology in the conserved domains and is clearly part of the SCAD superfamily despite the insertion of a large peptide between conserved domains. Alignment of the product of the Leishmania methotrexate resistance gene HMTX showed that an internal, highly conserved domain can be substituted by an unrelated sequence without loss of biological activity. Furthermore, comparisons of the chimeric trifunctional enzyme enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-hydroxyacyl-CoA epimerase with other family members suggests that the region between the conserved B and C domains is the last to diverge between closely related enzymes and that the F domain appears to evolve with a different evolutionary clock to the rest of the protein. Finally, a highly conserved pattern of serine and threonine residues in the active site of SCAD enzymes indicates that these residues may play an important role in catalysis. These observations should facilitate alignment of future members of the SCAD superfamily.
Krozowski
Z
Z
Laboratory of Molecular Hypertension, Baker Institute of Medical Research, Australia.
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000429:Alcohol Oxidoreductases / Q000235:genetics; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D005075:Biological Evolution; D017124:Conserved Sequence; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000235:genetics; D007891:Leishmania / Q000235:genetics; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D015067:17-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000426:Alcohol Dehydrogenase; D000449:Aldehyde Reductase; D006884:Hydroxybutyrate Dehydrogenase