Alcohol and polyol dehydrogenases are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type.

Abstract

Sorbitol dehydrogenase from sheep liver shows similarities to mammalian and yeast alcohol dehydrogenases.Comparisons based on peptides from segments of sorbitol dehydrogenase reveal that homologous regions with 38% identity include two ligands to the active site zinc atom in liver alcohol dehydrogenase, as well as further important residues. Similarities in other regions are less extensive, exactly as they are between different alcohol dehydrogenases. In all aspects, sorbitol dehydrogenase appears as a typical member of the alcohol dehydrogenase family. On the other hand, alcohol dehydrogenase from Drosophila, which has a shorter subunit, is not closely related to either of these enzymes, except for a region that probably corresponds to the first part ofthe coenzyme binding domain in many dehydrogenases. Instead, Drosophila alcohol dehydrogenase in its supposed catalytic region shows similarities toward Klebsiea ribitol dehydrogenase, which also has a small subunit. It may be concluded that both alcohol and polyol dehydrogenases show two types of protein subunit, reflecting an early subdivision of polypeptide types into "long" and "short" subunits rather than into different enzymatic specificities or quaternary structures. The relationships explain Imown properties of all these enzymes and provide insight into functional mechanisms and evolutionary interpretations.Sorbitol dehydrogenase (SDH) has some structural properties resembling those of mammalian and yeast alcohol dehydrogenases (ADHs) (1). All these enzymes have subunits ofsimilar size range, are sensitive to the same types of inhibitor, and contain reactive cysteine residues in similar structures, including one ofthe zinc ligands at the active site ofhorse liver ADH (LADH), 4226The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

Structure of the Drosophila melanogaster Glutathione‐Dependent Formaldehyde Dehydrogenase/Octanol Dehydrogenase Gene (Class III Alcohol Dehydrogenase)

“…Thus the present structure of gfd/odh would be more consistent with the presence of early introns removed by retrotranscriptional-recombinational events than with a model invoking identical intron insertions proceeding orderly towards the 3' end of the gene. Sequence alignments of ADH have illustrated the evolutionary relationships among the enzymes, which have led to the hypothesis of original molecular building blocks of the alcohol dehydrogenase families (Jornvall et al, 1981(Jornvall et al, , 1993Danielsson et al, 1994). The Rossmann fold of the coenzyme-binding domain of dehydrogenases (Rossmann et al, 1974), constitutes one of the best documented examples of these potential building units.…”

Critical Residues for Structure and Catalysis in Short-chain Dehydrogenases/Reductases

“…Since the discovery of fundamental differences between insect-type and liver-type alcohol dehydrogenases (1), corresponding to the protein families of "short-chain" dehydrogenases/reductases (SDR) 1 and "medium-chain" dehydrogenases/ reductases (MDR), respectively, SDR enzymes have received much attention. They constitute a large protein family with well over 2000 annotated enzyme and species variant sequences in databases and are represented in all life forms with minimally 60 genes found in the human genome (2)(3)(4).…”

Molecular Cloning and Characterization of Hemolymph 3-Dehydroecdysone 3β-Reductase from the Cotton Leafworm,Spodoptera littoralis

“…It has long been recognized that oxidoreductases, dependent upon nicotinamide coenzymes, can be divided into two extended superfamilies, according to their structural type and catalytic mechanism (20). The enzymes of one superfamily contain catalytically important zinc, many utilizing primary alcohols as substrates, though use of secondary alcohols and other activities are also noticed (21)(22)(23)(24).…”