title: Linking of isozyme and class variability patterns in the emergence of novel alcohol dehydrogenase functions. Characterization of isozymes in Uromastix hardwickii.
abstract: The nature of the isozyme differences in the class-I alcohol dehydrogenase structure from the lizard, Uromastix hardwickii, was determined and related to those in the human and horse enzymes, for which isozyme structures have also been established. The Uromastix isozymes differ much (at a total of 72 positions, 19%) but, in spite of this, have similar properties and were not obtained resolved. Their structures were analyzed in mixture, and the two sub-sets of peptides obtained could be distinguished by evaluation of the recovery ratios within the peptide pairs. The isozymes have class-I activities, with an ethanol dehydrogenase activity of 0.6 U/mg and no formaldehyde dehydrogenase activity, have typical class-I structures, and are composed of N-terminally acetylated 375-residue subunits (a and b). Importantly, variability patterns between the isozymes are reminiscent of those both in the other two lines with isozymes (primates and horse) and in the class distinctions of the enzyme. Hence, the variability pattern since the distant stage of class-I emergence is also visible within the more recent isozyme divergence, illustrating a continuity in the evolution of isozymes to classes (and then to enzymes). The pattern also links the different levels of multiplicity and may suggest an acceptability in common to duplications and mutations, compatible with the emergence of novel functions.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Hjelmqvist
authors.forename: J
authors.initials: J
authors.lastname: Shafqat
authors.forename: A R
authors.initials: AR
authors.lastname: Siddiqi
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008116:Lizards / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010449:Peptide Mapping; D017434:Protein Structure, Tertiary
chemical_list: D007527:Isoenzymes; D000426:Alcohol Dehydrogenase