View source for 8tzd


==Cryo-EM structure of bovine concentrative nucleoside transporter 3 in complex with Molnupiravir, condition 1, INT1-INT1-OFS conformation (3DVA analysis)==
<StructureSection load='8tzd' size='340' side='right'caption='[[8tzd]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tzd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TZD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8tzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tzd OCA], [https://pdbe.org/8tzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tzd RCSB], [https://www.ebi.ac.uk/pdbsum/8tzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tzd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F1MGR1_BOVIN F1MGR1_BOVIN] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:38418906</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8tzd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Lee S-Y]]
[[Category: Wright NJ]]