+検索条件
-Structure paper
タイトル | Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT. |
---|---|
ジャーナル・号・ページ | EMBO Rep, Vol. 22, Issue 3, Page e51628, Year 2021 |
掲載日 | 2021年3月3日 |
著者 | Meinan Lyu / Chih-Chia Su / James W Kazura / Edward W Yu / |
PubMed 要旨 | 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 ...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. |
リンク | EMBO Rep / PubMed:33471955 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.18 - 2.78 Å |
構造データ | EMDB-21354, PDB-6vqq: EMDB-21355, PDB-6vqr: EMDB-24076, PDB-7mxy: |
化合物 | ChemComp-R7M: ChemComp-HV6: ChemComp-HOH: |
由来 |
|
キーワード | MEMBRANE PROTEIN / Transporter / TRANSPORT PROTEIN/INHIBITOR / PfFNT / Lactate transporter / PfFNT-MMV007839 complex / TRANSPORT PROTEIN-INHIBITOR complex |