The Evolution of Dehydrogenases and Kinase

Differences between Alcohol Dehydeogenases

“…If, therefore, both domain and inregister similarities are true, the two domains might have evolved by an ancestral gene duplication, after which products from different halves of the duplicated gene retained/acquired the characteristic folding [4] of the coenzyme-binding domains. This hypothesis could explain the origin of the catalytic domains and the apparent contradictions [4,5] in some previous comparisons. It is further extended below by a number of other structural coincidences between dehydrogenases.…”

“…The different coenzyme-binding domains have extensive similarities [2 -51, are composed of two 'mononucleotide-binding units' [2,4,5] and resemble tertiary structures in kinases and some other proteins [2,4,5,15 -171. Evolutionary connections have been concluded, and an old ancestral gene coding for the mononucleotidebinding unit has been suggested [2,4,5]. The catalytic domains of different dehydrogenases, on the other hand, show no similarities with each other (with one exception [18]), nor with the coenzyme-binding domains [2-51. Their origin is therefore unknown.…”

“…It may, however, also be noticed that there is some variation in the tertiary structures concerned [4], that foldings of similar types occur in many proteins [4,19,20] and that it is difficult to judge directly the ancestral significance of suggested genetic codon variabilities [4,5], since effects of functional requirements are unknown (cf. [21,22]).…”

“…Furthermore, the evolutions of the catalytic domains and their different positions in the protein chains are not explained. Finally, some previous comparisons [23 -281, not based on present knowledge, have been questioned [4,5]. From all these aspects, the structure of yeast alcohol dehydrogenase is important, since it is sufficiently conserved to show the connection with other alcohol dehydrogenases but still dissimilar enough to give more general information on the type of evolutionary changes that occur in dehydrogenases.…”

Cholesterol Oxidase: Source,Properties and Applications.

“…A consensus sequence composed of repeating glycine residues (GXGXXG) followed by presence of aspartic acid or glutamic acid approximately 20 residues further is characteristic of a nucleotide-binding fold in most of the flavor enzymes [22]. In case of noncovalent form of CHOx, an almost identical consensus sequence of glycine moieties (G17-X-G19-X-G21-G⁄ A22) followed by a glutamate (E40) is present which shows the presence of nucleotide-binding fold.…”