8tz4

Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with GS-441524, subset reconstruction

spinqualitylabelsall models 8tz4, resolution 3.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tz4 is a 3 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.23Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F1MGR1_BOVIN Publication Abstract from PubMed Nucleoside analogs have broad clinical utility as antiviral drugs. Key to their systemic distribution and cellular entry are human nucleoside transporters. Here, we establish that the human concentrative nucleoside transporter 3 (CNT3) interacts with antiviral drugs used in the treatment of coronavirus infections. We report high-resolution single-particle cryo-electron microscopy structures of bovine CNT3 complexed with antiviral nucleosides N(4)-hydroxycytidine, PSI-6206, GS-441524 and ribavirin, all in inward-facing states. Notably, we found that the orally bioavailable antiviral molnupiravir arrests CNT3 in four distinct conformations, allowing us to capture cryo-electron microscopy structures of drug-loaded outward-facing and drug-loaded intermediate states. Our studies uncover the conformational trajectory of CNT3 during membrane transport of a nucleoside analog antiviral drug, yield new insights into the role of interactions between the transport and the scaffold domains in elevator-like domain movements during drug translocation, and provide insights into the design of nucleoside analog antiviral prodrugs with improved oral bioavailability. Antiviral drug recognition and elevator-type transport motions of CNT3.,Wright NJ, Zhang F, Suo Y, Kong L, Yin Y, Fedor JG, Sharma K, Borgnia MJ, Im W, Lee SY Nat Chem Biol. 2024 Sep;20(9):1144-1153. doi: 10.1038/s41589-024-01559-8. Epub , 2024 Feb 28. PMID:38418906 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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