Diversity of vertebrate class I alcohol dehydrogenase. Mammalian and non-mammalian enzyme functions correlated through the structure of a ratite enzyme.
Class I alcohol dehydrogenase has been characterized from ostrich liver in order to evaluate enzyme variability between two independent lines, mammalian forms of class I alcohol dehydrogenase as a group, and a sufficient number of the enzyme from the most recent animal class (Aves, birds) as another. Between the two enzyme groups, patterns are consistent and mutually similar. This indicates conserved metabolic and catalytic properties of class I alcohol dehydrogenase, suggesting its metabolic role to be distinct, in spite of its protein variability. The new structure has a microheterogeneity (position 112, Arg/Cys) in a variable Zn-binding loop. In addition, it also establishes further native variants at active-site positions, including one thus far unique residue at the inner part of the substrate-binding pocket (Ala141), and a replacement at position 271 (giving His271), which is also the site of a human alcohol dehydrogenase gamma 1/gamma 2 isozyme variability. The data correlate with functional differences in catalytic properties, the ostrich enzyme having a comparatively high Km for ethanol (5.9 mM at pH 10), and emphasize the importance of single positions in substrate and coenzyme binding, paralleling isozyme variability with protein variability within the class I enzymes.
Estonius
M
M
Department of Medical Biochemistry and Biophysics, Karolinska institutet, Stockholm, Sweden.
Hjelmqvist
L
L
Jörnvall
H
H
D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds; D017124:Conserved Sequence; D014644:Genetic Variation; D006736:Horses; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008322:Mammals / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010215:Papio; D010802:Phylogeny; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014714:Vertebrates / Q000235:genetics*
D007527:Isoenzymes; D000426:Alcohol Dehydrogenase