Fundamental molecular differences between alcohol dehydrogenase classes.

• DOI: 10.1073/pnas.91.11.4980
• Publication Date: 2006-05-31T12:47:09Z
• Authors: O Danielsson; S Atrian; T Luque; L Hjelmqvist; R Gonzàlez-Duarte; H Jörnvall
• Keywords: Formaldehyde dehydrogenase

Two types of alcohol dehydrogenase in separate protein families are the "medium-chain" zinc enzymes (including classical liver and yeast forms) "short-chain" insect form). Although medium-chain family has been characterized prokaryotes many eukaryotes (fungi, plants, cephalopods, vertebrates), insects have seemed to possess only short-chain enzyme. We now also a Drosophila. The enzyme is identical octanol dehydrogenase. It typical class III dehydrogenase, similar corresponding human form (70% residue identity), with mostly same residues involved substrate coenzyme interactions. Changes that do occur conservative, but Phe-51 functional interest relation decreased binding increased overall activity. Extra versus near position 250 affect coenzyme-binding domain. Enzymatic properties similar--i.e., very low activity toward ethanol (Km beyond measurement) high selectivity for formaldehyde/glutathione (S-hydroxymethylglutathione; kcat/Km = 160,000 min-1.mM-1). Between present ethanol-active I enzymes, however, patterns variability differ greatly, highlighting fundamentally molecular these two dehydrogenases, resembling general showing variation. gene coding Drosophila produces an mRNA about 1.36 kb at all developmental stages fly, compatible constitutive nature vertebrate Taken together, results bridge previously apparent gap distribution dehydrogenases establish strictly conserved enzyme, consistent important role this cellular metabolism.