8jy6

Structure of TbAQP2 in complex with anti-trypanosomatid drug melarsoprol

spinqualitylabelsall models 8jy6, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jy6 is a 4 chain structure with sequence from Trypanosoma brucei brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Ligands: L1U Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6ZXT3_TRYBB Publication Abstract from PubMed 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. Structural insights into drug transport by an aquaglyceroporin.,Chen W, Zou R, Mei Y, Li J, Xuan Y, Cui B, Zou J, Wang J, Lin S, Zhang Z, Wang C Nat Commun. 2024 May 11;15(1):3985. doi: 10.1038/s41467-024-48445-4. PMID:38734677 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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