7wn1: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
Line 8: Line 8:
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wn1 OCA], [https://pdbe.org/7wn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wn1 RCSB], [https://www.ebi.ac.uk/pdbsum/7wn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wn1 ProSAT]</span></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=7wn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wn1 OCA], [https://pdbe.org/7wn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wn1 RCSB], [https://www.ebi.ac.uk/pdbsum/7wn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wn1 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
<div style="background-color:#fffaf0;">
[https://www.uniprot.org/uniprot/Q9NIH7_PLAFA Q9NIH7_PLAFA]
== Publication Abstract from PubMed ==
By lacking de novo purine biosynthesis enzymes, Plasmodium falciparum requires purine nucleoside uptake from host cells. The indispensable nucleoside transporter ENT1 of P. falciparum facilitates nucleoside uptake in the asexual blood stage. Specific inhibitors of PfENT1 prevent the proliferation of P. falciparum at submicromolar concentrations. However, the substrate recognition and inhibitory mechanism of PfENT1 are still elusive. Here, we report cryo-EM structures of PfENT1 in apo, inosine-bound, and inhibitor-bound states. Together with in vitro binding and uptake assays, we identify that inosine is the primary substrate of PfENT1 and that the inosine-binding site is located in the central cavity of PfENT1. The endofacial inhibitor GSK4 occupies the orthosteric site of PfENT1 and explores the allosteric site to block the conformational change of PfENT1. Furthermore, we propose a general "rocker switch" alternating access cycle for ENT transporters. Understanding the substrate recognition and inhibitory mechanisms of PfENT1 will greatly facilitate future efforts in the rational design of antimalarial drugs.
 
Structural basis of the substrate recognition and inhibition mechanism of Plasmodium falciparum nucleoside transporter PfENT1.,Wang C, Yu L, Zhang J, Zhou Y, Sun B, Xiao Q, Zhang M, Liu H, Li J, Li J, Luo Y, Xu J, Lian Z, Lin J, Wang X, Zhang P, Guo L, Ren R, Deng D Nat Commun. 2023 Mar 28;14(1):1727. doi: 10.1038/s41467-023-37411-1. PMID:36977719<ref>PMID:36977719</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wn1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
Retrieved from "https://proteopedia.org/7wn1"