Evolution of substrate specificity in the Nucleobase-Ascorbate Transporter (NAT) protein family

Microbial Cell
Anezia KourkoulouGeorge Diallinas

Abstract

L-ascorbic acid (vitamin C) is an essential metabolite in animals and plants due to its role as an enzyme co-factor and antioxidant activity. In most eukaryotic organisms, L-ascorbate is biosynthesized enzymatically, but in several major groups, including the primate suborder Haplorhini, this ability is lost due to gene truncations in the gene coding for L-gulonolactone oxidase. Specific ascorbate transporters (SVCTs) have been characterized only in mammals and shown to be essential for life. These belong to an extensively studied transporter family, called Nucleobase-Ascorbate Transporters (NAT). The prototypic member of this family, and one of the most extensively studied eukaryotic transporters, is UapA, a uric acid-xanthine/H+ symporter in the fungus Aspergillus nidulans. Here, we investigate molecular aspects of NAT substrate specificity and address the evolution of ascorbate transporters apparently from ancestral nucleobase transporters. We present a phylogenetic analysis, identifying a distinct NAT clade that includes all known L-ascorbate transporters. This clade includes homologues only from vertebrates, and has no members in non-vertebrate or microbial eukaryotes, plants or prokaryotes. Additionally, we identify withi...Continue Reading

Citations

Jun 20, 2019·Open Biology·Emmanuel Mikros, George Diallinas
Mar 8, 2020·Medicinal Research Reviews·Gustavo D Campagnaro, Harry P de Koning
Mar 22, 2020·Molecular Microbiology·Maria BotouStathis Frillingos
Jan 27, 2021·Journal of Molecular Biology·Anezia KourkoulouGeorge Diallinas
Apr 28, 2021·Trends in Biochemical Sciences·George Diallinas

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Methods Mentioned

BETA
Phylogenetic profile
PCR

Software Mentioned

Ensembl
ProtTest
MAFFT
MEGA
RAxML
APR
HHpred
MUSCLE
Ensembl Metazoa
FigTree

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