7MXY

Cryo-EM structure of PfFNT-inhibitor complex

7MXY の概要

• エントリーDOI: 10.2210/pdb7mxy/pdb
• EMDBエントリー: 24076
• 分子名称: Formate-nitrite transporter, (Z)-4,4,5,5,5-pentakis(fluoranyl)-1-(4-methoxy-2-oxidanyl-phenyl)-3-oxidanyl-pent-2-en-1-one (3 entities in total)
• 機能のキーワード: pffnt, lactate transporter, pffnt-mmv007839 complex, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 174022.35

構造登録者

Yu, E.W.,Su, C.,Lyu, M. (登録日: 2021-05-19, 公開日: 2021-12-08, 最終更新日: 2025-06-04)

主引用文献

Lyu, M.,Su, C.,Kazura, J.W.,Yu, E.W.
Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT
EMBO Rep, 22:e51628-, 2021

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: 33471955
DOI: 10.15252/embr.202051628

実験手法

ELECTRON MICROSCOPY (2.18 Å)