Avian alcohol dehydrogenase. Characterization of the quail enzyme, functional interpretations, and relationships to the different classes of mammalian alcohol dehydrogenase

• Published in: Biochemistry (Easton) 1990-09, Vol.29 (36), p.8365-8371
• Main Authors: Kaiser, Rudolf, Nussrallah, Barbara, Dam, Richard, Wagner, Fred W, Jörnvall, Hans
• Format: Article
• Language: English
• Subjects: Alcohol Dehydrogenase - classification; Alcohol Dehydrogenase - genetics; Alcohol Dehydrogenase - isolation & purification; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding Sites; Biological and medical sciences; Coturnix japonica; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; liver; Liver - enzymology; Mammals - metabolism; Molecular Sequence Data; Multigene Family; Oxidoreductases; Quail - genetics; Quail - metabolism; Sequence Alignment; Sequence Homology, Nucleic Acid; Species Specificity; Zinc
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00488a024

The primary structure of the major quail liver alcohol dehydrogenase was determined. It is a long-chain, zinc-containing alcohol dehydrogenase of the type occurring also in mammals and hence allows judgement of the gene duplications giving rise to the classes of the human alcohol dehydrogenase system. The avian form is most closely related to the class I mammalian enzyme (72-75% residue identity), least related to class II (60% identity), and intermediately related to class III (64-65% identity). This pattern distinguishes the mammalian enzyme classes and separates classes I and II in particular. In addition to the generally larger similarities with class I, the avian enzyme exhibits certain residue patterns otherwise typical of the other classes, including an extra Trp residue, present in both class II and III but not in class I, with a corresponding increase in the UV absorbance. The avian enzyme further shows that a Gly residue at position 260 previously considered strictly conserved in alcohol dehydrogenases can be exchanged with Lys. However, zinc-binding residues, coenzyme-binding residues, and to a large extent substrate-binding residues are unchanged in the avian enzyme, suggesting its functional properties to be related to those of the class I mammalian alcohol dehydrogenases. In contrast, the areas of subunit interactions in the dimers differ substantially. These results show that (a) the vertebrate enzyme classes are of distant origin, (b) the submammalian enzyme exhibits partly mixed properties in relation to the classes, and (c) the three mammalian enzyme classes are not as equidistantly related as initially apparent but suggest origins from two sublevels.