View source for 9qo9


==Inward-occluded structure of human GABA transporter 3 bound to substrate GABA==
<StructureSection load='9qo9' size='340' side='right'caption='[[9qo9]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qo9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QO9 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=9qo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qo9 OCA], [https://pdbe.org/9qo9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qo9 RCSB], [https://www.ebi.ac.uk/pdbsum/9qo9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qo9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S6A11_HUMAN S6A11_HUMAN] Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:7874447). Can also mediate transport of beta-alanine and to a lower extent that of taurine and hypotaurine (By similarity).[UniProtKB:P31650]<ref>PMID:7874447</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The astrocytic gamma-aminobutyric acid (GABA) transporter, GAT3, is essential for terminating GABAergic signaling in the central nervous system. Selective inhibition of GAT3 offers a potential strategy for elevating extracellular GABA levels for the treatment of neurological disorders including epilepsy. However, few potent and selective GAT3 inhibitors have been developed, and their mechanisms of inhibition remain poorly understood. Here, we present the cryo-electron microscopy structures of full-length, wild-type human GAT3, hGAT3, bound to a selective inhibitor, to substrate GABA, or in substrate-free state. hGAT3 bound to the inhibitor or in the substrate-free state exhibits an inward-open conformation. The inhibitor binds within the intracellular permeation pathway, positioned between transmembrane helices 1, 2, 3, 6, 7, and 8. The GABA-bound hGAT3 is captured in an inward-occluded state, revealing the ion coordination and substrate recognition network, including a cation-pi interaction between GABA's gamma-amino group and a phenylalanine residue in transmembrane helix 6. Our data reveal the molecular determinants for the inhibitor selectivity, and the mode of substrate binding and transport inhibition, providing blueprints for the rational design of next-generation selective GAT3 inhibitors.

Structural basis for selective inhibition of human GABA transporter GAT3.,Mortensen JS, Bavo F, Jensen MH, Pedersen APS, Storm JP, Pape T, Frolund B, Wellendorph P, Shahsavar A Nat Commun. 2026 Jan 29;17(1):1774. doi: 10.1038/s41467-026-68479-0. PMID:41611703<ref>PMID:41611703</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qo9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bavo F]]
[[Category: Frolund B]]
[[Category: Jensen MH]]
[[Category: Mortensen JS]]
[[Category: Pape T]]
[[Category: Pedersen APS]]
[[Category: Shahsavar A]]
[[Category: Storm JP]]
[[Category: Wellendorph P]]