Nucleobase transporters

Abstract

Purines and pyrimidines play a key role in nucleic acid and nucleotide metabolism of all cells. In addition, they can be used as nitrogen sources in plants and many microorganisms. Transport of nucleobases across biological membranes is mediated by specific transmembrane transport proteins. Nucleobase transporters have been identified genetically and/or physiologically in bacteria, fungi, protozoa, algae, plants and mammals. A limited number of bacterial and fungal transporter genes have been cloned and analysed in great detail at the molecular level. Very recently, nucleobase transporters have been identified in plants. In other systems, with less accessible genetics, such as vertebrates and protozoa, no nucleobase transporter genes have been identified, and the transporters have been characterized and classified by physiological and biochemical approaches instead. In this review, it is shown that nucleobase transporters and similar sequences of unknown function present in databases constitute three basic families, which will be designated NAT, PRT and PUP. The first includes members from archea, eubacteria, fungi, plants and metazoa, the second is restricted to prokaryotes and fungi, and the last one is only found in plants. Interestingly, mammalian ascorbate transporters are homologous to NAT sequences. The function of different nucleobase transporters is also described, as is how their expression is regulated and what is currently known about their structure-function relationships. Common features emerging from these studies are expected to prove critical in understanding what governs nucleobase transporter specificity and in selecting proper model microbial systems for cloning and studying plant, protozoan and mammalian nucleobase transporters of agricultural, pharmacological and medical importance.

Nucleobase and nucleoside transport and integration into plant metabolism

“…The nucleobase-ascorbate transporter (NAT) family, belonging to the nucleobase:cation symporter 2 (NCS2) family, represents the largest and most conserved class of nucleobase transporters (De Koning and Diallinas, 2000). It includes more than 2000 putative members in all major taxa of organisms like eubacteria, archea, filamentous fungi, plants, insects, nematodes, mammals and humans (De Koning and Diallinas, 2000; Frillingos, 2012).…”

“…It includes more than 2000 putative members in all major taxa of organisms like eubacteria, archea, filamentous fungi, plants, insects, nematodes, mammals and humans (De Koning and Diallinas, 2000; Frillingos, 2012). Remarkably, most protozoa and Saccharomyces cerevisiae do not possess NAT proteins and only a few NAT proteins have been biochemically characterized so far (Frillingos, 2012).…”

Uptake of purines in Plasmodium falciparum-infected human erythrocytes is mostly mediated by the human Equilibrative Nucleoside Transporter and the human Facilitative Nucleobase Transporter

“…The hFNT1 nucleobase transporter is the only route of uptake for adenine and hypoxanthine in human erythrocytes [6,21] and it was next investigated whether this transporter is inhibited by inhibitors of the NPP. Like hENT1-mediated [ 3 H]-uridine uptake, hFNT1-mediated [ 3 H]-adenine uptake was not inhibited by NPPB at up to 1 mM (n = 3; Figure 4B).…”

“…Non-infected human erythrocytes take up nucleosides through the human equilibrative nucleoside transporter hENT1 [4] and purine bases through the facilitative nucleobase transporter hFNT1 [5,6]. hENT1, but not hFNT1, is potently inhibited by 6-[(nitrobenzyl)-thio]9-β- d -ribofuranosylpurine (NBMPR) [7].…”

ProBLM Web Server: Protein and Membrane Placement and Orientation Package

“…They serve as ion channels [3], ion pumps [4], and transporters [5] among other functions [6]. Due to the importance of membrane proteins, they are one of the primary targets for drug discovery [7, 8].…”