Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Antiviral drug recognition and elevator-type transport motions of CNT3.
Journal, issue, pages	Nat Chem Biol, Year 2024
Publish date	Feb 28, 2024
Authors	Nicholas J Wright / Feng Zhang / Yang Suo / Lingyang Kong / Ying Yin / Justin G Fedor / Kedar Sharma / Mario J Borgnia / Wonpil Im / Seok-Yong Lee /
PubMed Abstract	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 ...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-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.
External links	Nat Chem Biol / PubMed:38418906
Methods	EM (single particle)
Resolution	2.31 - 6.92 Å
Structure data	41730 8tz1 EMDB-41730, PDB-8tz1: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Ribavirin Method: EM (single particle) / Resolution: 2.54 Å 41731 8tz2 EMDB-41731, PDB-8tz2: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in MSP2N2 nanodiscs, apo state Method: EM (single particle) / Resolution: 2.8 Å 41732 8tz3 EMDB-41732, PDB-8tz3: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with GS-441524, consensus reconstruction Method: EM (single particle) / Resolution: 2.31 Å 41733 8tz4 EMDB-41733, PDB-8tz4: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with GS-441524, subset reconstruction Method: EM (single particle) / Resolution: 3.23 Å 41734 8tz5 EMDB-41734, PDB-8tz5: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with N-hydroxycytidine Method: EM (single particle) / Resolution: 2.74 Å 41735 8tz6 EMDB-41735, PDB-8tz6: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with PSI-6206 Method: EM (single particle) / Resolution: 2.69 Å 41736 8tz7 EMDB-41736, PDB-8tz7: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-INT1 conformation Method: EM (single particle) / Resolution: 3.0 Å 41737 8tz8 EMDB-41737, PDB-8tz8: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-INT3 conformation Method: EM (single particle) / Resolution: 3.19 Å 41738 8tz9 EMDB-41738, PDB-8tz9: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT2-INT2-INT2 conformation Method: EM (single particle) / Resolution: 3.67 Å 41739 8tza EMDB-41739, PDB-8tza: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT2-INT1-INT1 conformation Method: EM (single particle) / Resolution: 3.43 Å EMDB-41740: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, consensus reconstruction Method: EM (single particle) / Resolution: 2.8 Å EMDB-41741: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-OFS-OFS conformation Method: EM (single particle) / Resolution: 6.92 Å EMDB-41742: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-OFS-INT1 conformation Method: EM (single particle) / Resolution: 4.16 Å EMDB-41743: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-OFS-INT3 conformation Method: EM (single particle) / Resolution: 5.72 Å EMDB-41744: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-OFS conformation (from ensemble analysis) Method: EM (single particle) / Resolution: 3.4 Å EMDB-41745: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT3-INT3-OFS conformation Method: EM (single particle) / Resolution: 4.28 Å EMDB-41746: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT3-INT3-INT1 conformation Method: EM (single particle) / Resolution: 3.47 Å EMDB-41747: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT3-INT3-INT3 conformation Method: EM (single particle) / Resolution: 4.3 Å EMDB-41748: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-INT1-INT3 (clockwise) conformation Method: EM (single particle) / Resolution: 3.87 Å EMDB-41749: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, OFS-INT1-INT3 (counterclockwise) conformation Method: EM (single particle) / Resolution: 3.68 Å EMDB-41750: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT2-INT2-INT1 conformation Method: EM (single particle) / Resolution: 3.49 Å EMDB-41751: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, INT1-INT1-INT1 conformation Method: EM (single particle) / Resolution: 3.45 Å EMDB-41752: Cryo-EM reconstruction of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 2, consensus reconstruction Method: EM (single particle) / Resolution: 2.99 Å 41755 8tzd EMDB-41755, PDB-8tzd: Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-OFS conformation (3DVA analysis) Method: EM (single particle) / Resolution: 3.2 Å
Chemicals	ChemComp-RBV: 1-(beta-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide / medication, antivirusYM / Ribavirin ChemComp-NA: Unknown entry ChemComp-LBN: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / phospholipidYM / POPC ChemComp-HOH: WATER / Water ChemComp-U08: (2~{R},3~{R},4~{S},5~{R})-2-(4-azanylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolane-2-carbonitrile / antivirusYM / GS-441524 ChemComp, No image ChemComp-U56: Unknown entry ChemComp, No image ChemComp-U7I: Unknown entry ChemComp, No image ChemComp-XMO*: Unknown entry
Source	bos taurus (cattle)
Keywords	TRANSPORT PROTEIN / membrane protein / transporter / nucleoside