6VQR
CryoEM Structure of the PfFNT-inhibitor complex
Summary for 6VQR
| Entry DOI | 10.2210/pdb6vqr/pdb |
| EMDB information | 21355 |
| Descriptor | Formate-nitrite transporter, (2R)-2-hydroxy-7-methoxy-2-(pentafluoroethyl)-2,3-dihydro-4H-1-benzopyran-4-one (2 entities in total) |
| Functional Keywords | transporter, membrane protein |
| Biological source | Plasmodium falciparum (isolate 3D7) |
| Total number of polymer chains | 5 |
| Total formula weight | 174022.35 |
| Authors | |
| Primary citation | Lyu, M.,Su, C.C.,Kazura, J.W.,Yu, E.W. Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT. Embo Rep., 22:e51628-e51628, 2021 Cited by PubMed Abstract: The intra-erythrocyte stage of P. falciparum relies primarily on glycolysis to generate adenosine triphosphate (ATP) and the energy required to support growth and reproduction. Lactic acid, a metabolic byproduct of glycolysis, is potentially toxic as it lowers the pH inside the parasite. Plasmodium falciparum formate-nitrite transporter (PfFNT), a 34-kDa transmembrane protein, has been identified as a novel drug target as it exports lactate from inside the parasite to the surrounding parasitophorous vacuole within the erythrocyte cytosol. The structure and detailed molecular mechanism of this membrane protein are not yet available. Here we present structures of PfFNT in the absence and presence of the functional inhibitor MMV007839 at resolutions of 2.56 Å and 2.78 Å using single-particle cryo-electron microscopy. Genetic analysis and transport assay indicate that PfFNT is able to transfer lactate across the membrane. Combined, our data suggest a stepwise displacement mechanism for substrate transport. The PfFNT membrane protein is capable of picking up lactate ions from the parasite's cytosol, converting them to lactic acids and then exporting these acids into the extracellular space. PubMed: 33471955DOI: 10.15252/embr.202051628 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.78 Å) |
Structure validation
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