8JY7

Structure of the TbAQP2 in the apo conformation

8JY7 の概要

• エントリーDOI: 10.2210/pdb8jy7/pdb
• EMDBエントリー: 36722
• 分子名称: Aquaglyceroporin 2 (1 entity in total)
• 機能のキーワード: aquaporin, membrane protein
• 由来する生物種: Trypanosoma brucei brucei
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 147103.66

構造登録者

Chen, W.,Wang, C. (登録日: 2023-07-03, 公開日: 2024-05-29, 最終更新日: 2025-07-16)

主引用文献

Chen, W.,Zou, R.,Mei, Y.,Li, J.,Xuan, Y.,Cui, B.,Zou, J.,Wang, J.,Lin, S.,Zhang, Z.,Wang, C.
Structural insights into drug transport by an aquaglyceroporin.
Nat Commun, 15:3985-3985, 2024

PubMed Abstract: Pentamidine and melarsoprol are primary drugs used to treat the lethal human sleeping sickness caused by the parasite Trypanosoma brucei. Cross-resistance to these two drugs has recently been linked to aquaglyceroporin 2 of the trypanosome (TbAQP2). TbAQP2 is the first member of the aquaporin family described as capable of drug transport; however, the underlying mechanism remains unclear. Here, we present cryo-electron microscopy structures of TbAQP2 bound to pentamidine or melarsoprol. Our structural studies, together with the molecular dynamic simulations, reveal the mechanisms shaping substrate specificity and drug permeation. Multiple amino acids in TbAQP2, near the extracellular entrance and inside the pore, create an expanded conducting tunnel, sterically and energetically allowing the permeation of pentamidine and melarsoprol. Our study elucidates the mechanism of drug transport by TbAQP2, providing valuable insights to inform the design of drugs against trypanosomiasis.

PubMed: 38734677
DOI: 10.1038/s41467-024-48445-4

実験手法

ELECTRON MICROSCOPY (3.2 Å)