Abstract
BackgroundAlcohol dehydrogenase (ADH) activity is widely distributed in the three domains of life. Currently, there are three non-homologous NAD(P)+-dependent ADH families reported: Type I ADH comprises Zn-dependent ADHs; type II ADH comprises short-chain ADHs described first in Drosophila; and, type III ADH comprises iron-containing ADHs (FeADHs). These three families arose independently throughout evolution and possess different structures and mechanisms of reaction. While types I and II ADHs have been extensively studied, analyses about the evolution and diversity of (type III) FeADHs have not been published yet. Therefore in this work, a phylogenetic analysis of FeADHs was performed to get insights into the evolution of this protein family, as well as explore the diversity of FeADHs in eukaryotes.Principal FindingsResults showed that FeADHs from eukaryotes are distributed in thirteen protein subfamilies, eight of them possessing protein sequences distributed in the three domains of life. Interestingly, none of these protein subfamilies possess protein sequences found simultaneously in animals, plants and fungi. Many FeADHs are activated by or contain Fe2+, but many others bind to a variety of metals, or even lack of metal cofactor. Animal FeADHs are found in just one protein subfamily, the hydroxyacid-oxoacid transhydrogenase (HOT) subfamily, which includes protein sequences widely distributed in fungi, but not in plants), and in several taxa from lower eukaryotes, bacteria and archaea. Fungi FeADHs are found mainly in two subfamilies: HOT and maleylacetate reductase (MAR), but some can be found also in other three different protein subfamilies. Plant FeADHs are found only in chlorophyta but not in higher plants, and are distributed in three different protein subfamilies.Conclusions/SignificanceFeADHs are a diverse and ancient protein family that shares a common 3D scaffold with a patchy distribution in eukaryotes. The majority of sequenced FeADHs from eukaryotes are distributed in just two subfamilies, HOT and MAR (found mainly in animals and fungi). These two subfamilies comprise almost 85% of all sequenced FeADHs in eukaryotes.
Highlights
Alcohol dehydrogenase (ADH) activity is widely distributed in numerous phyla, which include organisms belonging to the three domains of life [1,2]
The NCBI’s Conserved Domain Database [32] identify iron-dependent ADHs as members of DHQ-fide iron-dependent alcohol dehydrogenase (FeADH) protein superfamily, which comprises four related families: i) the dehydroquinate synthase-like family, which catalyzes the conversion of 3-deoxy-Darabino-heptulosonate-7-phosphate (DAHP) to dehydroquinate (DHQ) in the second step of the shikimate pathway; ii) the family of glycerol-1-phosphate dehydrogenase and related proteins; iii) the glycerol dehydrogenase-like family; and, iv) the iron-containing alcohol dehydrogenase-like family
Because glycerol dehydrogenases are reported as Zn-metallo-enzymes not containing iron [53,54], comprise a divergent branch with respect to the other iron-containing alcohol dehydrogenases (Fig 1), and conserve just one of the three conserved histidine residues involved in iron-binding (See 3.7 section), we centered the present analysis to the bona fide iron-dependent alcohol dehydrogenase (FeADH) protein family, as defined in the NCBI’s Conserved Domain Database
Summary
Alcohol dehydrogenase (ADH) activity is widely distributed in numerous phyla, which include organisms belonging to the three domains of life [1,2]. This activity is performed by different enzymes in different organisms. There are three non-homologous NAD(P)+-dependent ADH families reported: Type I ADH comprises Zn-dependent ADHs; type II ADH comprises short-chain ADHs described first in Drosophila; and, type III ADH comprises iron-containing ADHs (FeADHs). These three families arose independently throughout evolution and possess different structures and mechanisms of reaction. In this work, a phylogenetic analysis of FeADHs was performed to get insights into the evolution of this protein family, as well as explore the diversity of FeADHs in eukaryotes
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