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. 1987 May;84(9):2580–2584. doi: 10.1073/pnas.84.9.2580

Mammalian alcohol dehydrogenases of separate classes: intermediates between different enzymes and intraclass isozymes.

H Jörnvall, J O Höög, H von Bahr-Lindström, B L Vallee
PMCID: PMC304701  PMID: 3472225

Abstract

A comparison of the structure of class II human liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) (containing pi subunits) with those of the human class I isozymes (containing alpha, beta, and gamma subunits) reveals differences at about 40% of all positions. Variations are large for active-site regions, the segment around the second zinc atom, and for segments involved in subunit interactions. The two classes of alcohol dehydrogenase have diverged to exhibit structural differences to about half the extent of those between alcohol and polyol dehydrogenases. Hence, the two classes of alcohol dehydrogenase represent steps in enzyme rather than isozyme divergence. An evolutionary scheme that relates different types of zinc-containing mammalian dehydrogenases to one another encompasses at least three levels of gene duplication subsequent to the early step(s) of assembly of building unit(s). The first level of duplication results in the formation of now clearly different enzymes. The second level concerns the various classes of alcohol dehydrogenase, forming steps between typical enzymes and isozymes. The third level encompasses recent and multiple duplications in isozyme evolution of alcohol dehydrogenases. This scheme, linking zinc-containing dehydrogenases at different levels, resembles that in other protein families and reflects general patterns in protein relationships.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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