Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes.
The primary structure of class III alcohol dehydrogenase (dimeric with chi subunits) from human liver has been determined by peptide analyses. The protein chain is a clearly distinct type of subunit distantly related to those of both human class I and class II alcohol dehydrogenases (with alpha, beta, gamma, and pi subunits, respectively). Disregarding a few gaps, residue differences in the chi protein chain with respect to beta 1 and pi occur at 139 and 140 positions, respectively. Compared to class I, the 373-residue chi structure has an extra residue, Cys after position 60, and two missing ones, the first two residues relative to class I, although the N-terminus is acetylated like that for those enzymes. The chi subunit contains two more tryptophan residues than the class I subunits, accounting for the increased absorbance at 280 nm. There are also four additional acidic and two fewer basic side chains than in the class I beta structure, compatible with the markedly different electrophoretic mobility of the class III enzyme. Residue differences between class III and the other classes occur with nearly equal frequency in the coenzyme-binding and catalytic domains. The similarity in the number of exchanges relative to that of the enzymes of the other two classes supports conclusions that the three classes of alcohol dehydrogenase reflect stages in the development of separate enzymes with distinct functional roles. In spite of the many exchanges, the residues critical to basic functional properties are either completely unchanged--all zinc ligands and space-restricted Gly residues--or partly unchanged--residues at the coenzyme-binding pocket.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaiser
R
R
Department of Chemistry I, Karolinska Institutet, Stockholm, Sweden.
Holmquist
B
B
Hempel
J
J
Vallee
B L
BL
Jörnvall
H
H
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000595:Amino Acid Sequence; D003488:Cyanogen Bromide; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification
D007527:Isoenzymes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D000426:Alcohol Dehydrogenase; D003488:Cyanogen Bromide