Characteristics of mammalian class III alcohol dehydrogenases, an enzyme less variable than the traditional liver enzyme of class I.
Class III alcohol dehydrogenase, whose activity toward ethanol is negligible, has defined, specific properties and is not just a "variant" of the class I protein, the traditional liver enzyme. The primary structure of the horse class III protein has now been determined, and this allows the comparison of alcohol dehydrogenases from human, horse, and rat for both classes III and I, providing identical triads for both these enzyme types. Many consistent differences between the classes separate the two forms as distinct enzymes with characteristic properties. The mammalian class III enzymes are much less variable in structure than the corresponding typical liver enzymes of class I: there are 35 versus 84 positional differences in these identical three-species sets. The class III and class I subunits contain four versus two tryptophan residues, respectively. This makes the differences in absorbance at 280 nm a characteristic property. There are also 4-6 fewer positive charges in the class III enzymes accounting for their electrophoretic differences. The substrate binding site of class III differs from that of class I by replacements at positions that form the hydrophobic barrel typical for this site. In class III, two to four of these positions contain residues with polar or even charged side chains (positions 57 and 93 in all species, plus positions 116 in the horse and 140 in the human and the horse), while corresponding intraclass variation is small. All these structural features correlate with functional characteristics and suggest that the enzyme classes serve different roles. In addition, the replacements between these triad sets illustrate further general properties of the two mammalian alcohol dehydrogenase classes.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaiser
R
R
Department of Chemistry I, Karolinska Institutet, Stockholm, Sweden.
Holmquist
B
B
Vallee
B L
BL
Jörnvall
H
H
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D006736:Horses; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D000429:Alcohol Oxidoreductases; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases