Structural relationships among class I isozymes of human liver alcohol dehydrogenase.
The alpha subunit of human liver alcohol dehydrogenase has been submitted to structural analysis. Together with earlier work on the beta and gamma subunits, the results allow conclusions on the relationship of all known forms of the class I type of the enzyme. Two segments of the alpha subunit were determined; one was also reinvestigated in the beta and gamma subunits. The results establish 11 residue replacements among class I subunits in the segments analyzed and show that the alpha, beta, and gamma protein chains each are structurally distinct in the active site regions, where replacements affect positions influencing coenzyme binding (position 47; Gly in alpha, Arg in beta and gamma) and substrate specificity (position 48; Thr in alpha and beta, Ser in gamma). Residue 128, previously not detected in beta and gamma subunits, corresponds to a position of another isozyme difference (Arg in beta and gamma, Ser in alpha). The many amino acid replacements in alcohol dehydrogenases even at their active sites illustrate that in judgements of enzyme functions absolute importance of single residues should not be overemphasized. Available data suggest that alpha and gamma are the more dissimilar forms within the family of the three class I subunits that have resulted from two gene duplications. The class distinction of alcohol dehydrogenases previously suggested from enzymatic, electrophoretic, and immunological properties therefore also holds true in relation to their structures.
Hempel
J
J
Holmquist
B
B
Fleetwood
L
L
Kaiser
R
R
Barros-Söderling
J
J
Bühler
R
R
Vallee
B L
BL
Jörnvall
H
H
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000302:isolation & purification*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003488:Cyanogen Bromide; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification*; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000032:analysis
D007527:Isoenzymes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D003488:Cyanogen Bromide