View source for 8jy8


==Structure of TbAQP2 in complex with anti-trypanosomatid drug pentamidine==
<StructureSection load='8jy8' size='340' side='right'caption='[[8jy8]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jy8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JY8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JY8 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PNT:1,5-BIS(4-AMIDINOPHENOXY)PENTANE'>PNT</scene></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=8jy8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jy8 OCA], [https://pdbe.org/8jy8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jy8 RCSB], [https://www.ebi.ac.uk/pdbsum/8jy8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jy8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6ZXT3_TRYBB Q6ZXT3_TRYBB] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:38734677</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8jy8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Chen W]]
[[Category: Wang C]]