Diversity and Evolutionary Analysis of Iron-Containing (Type-III) Alcohol Dehydrogenases in Eukaryotes

PLoS One. 2016 Nov 28;11(11):e0166851. doi: 10.1371/journal.pone.0166851. eCollection 2016.

Abstract

Background: Alcohol 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 findings: Results 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/significance: FeADHs 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.

MeSH terms

  • Alcohol Dehydrogenase / chemistry
  • Alcohol Dehydrogenase / genetics*
  • Alcohol Dehydrogenase / metabolism*
  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism
  • Binding Sites
  • Eukaryota / enzymology*
  • Evolution, Molecular*
  • Humans
  • Iron / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Phylogeny*

Substances

  • Mitochondrial Proteins
  • Iron
  • Alcohol Oxidoreductases
  • Alcohol Dehydrogenase
  • hydroxyacid-oxoacid transhydrogenase
  • Oxidoreductases Acting on CH-CH Group Donors
  • maleylacetate reductase

Grants and funding

This work was supported by Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México, PAPIIT grants IN216513 and IN225016 to HRR, and Consejo Nacional de Ciencia y Tecnología (México), Ph.D. fellowship No. 233791, and Programa de Doctorado en Ciencias, Universidad Nacional Autónoma de México, to CGL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.