View source for 8jy7


==Structure of the TbAQP2 in the apo conformation==
<StructureSection load='8jy7' size='340' side='right'caption='[[8jy7]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jy7]] 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=8JY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JY7 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=8jy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jy7 OCA], [https://pdbe.org/8jy7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jy7 RCSB], [https://www.ebi.ac.uk/pdbsum/8jy7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jy7 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 8jy7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Chen W]]
[[Category: Wang C]]