title: Identity of a Plasmodium lactate/H(+) symporter structurally unrelated to human transporters.
abstract: Maintenance of a high glycolytic flow rate is critical for the rapid growth and virulence of malarial parasites. The parasites release two moles of lactic acid per mole of glucose as the anaerobic end product. However, the molecular identity of the Plasmodium lactate transporter is unknown. Here we show that a member of the microbial formate-nitrite transporter family, PfFNT, acts as a lactate/proton symporter in Plasmodium falciparum. Besides L-lactate, PfFNT transports physiologically relevant D-lactate, as well as pyruvate, acetate and formate, and is inhibited by the antiplasmodial compounds phloretin, furosemide and cinnamate derivatives, but not by p-chloromercuribenzene sulfonate (pCMBS). Our data on PfFNT monocarboxylate transport are consistent with those obtained with living parasites. Moreover, PfFNT is the only transporter of the plasmodial glycolytic pathway for which structure information is available from crystals of homologous proteins, rendering it amenable to further evaluation as a novel antimalarial drug target.
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Binghua
authors: B
authors: Wu
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Janis
authors: J
authors: Rambow
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Sinja
authors: S
authors: Bock
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Julia
authors: J
authors: Holm-Bertelsen
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Marie
authors: M
authors: Wiechert
authors: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany.
authors: Alexandra Blancke
authors: AB
authors: Soares
authors: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany.
authors: Tobias
authors: T
authors: Spielmann
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Eric
authors: E
authors: Beitz
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005453:Fluorescence; D006019:Glycolysis / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000469:parasitology; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010271:Parasites / Q000187:drug effects / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D011522:Protons; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D027981:Symporters / Q000737:chemistry / Q000378:metabolism*
chemical_list: D027501:Monocarboxylic Acid Transporters; D011522:Protons; D015800:Protozoan Proteins; D054852:Small Molecule Libraries; D027981:Symporters; D049452:Green Fluorescent Proteins; D019344:Lactic Acid