View source for 9wc6


==The structure of glycine transport 2 in complex with glycine==
<StructureSection load='9wc6' size='340' side='right'caption='[[9wc6]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wc6]] 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=9WC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WC6 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</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=9wc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wc6 OCA], [https://pdbe.org/9wc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wc6 RCSB], [https://www.ebi.ac.uk/pdbsum/9wc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wc6 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SC6A5_HUMAN SC6A5_HUMAN] Hereditary hyperekplexia. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SC6A5_HUMAN SC6A5_HUMAN] Sodium- and chloride-dependent glycine transporter (PubMed:10381548, PubMed:10606742, PubMed:16751771, PubMed:31370103, PubMed:9845349). Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals (PubMed:9845349). May be responsible for the termination of neurotransmission at strychnine-sensitive glycinergic synapses (PubMed:9845349).<ref>PMID:10381548</ref> <ref>PMID:10606742</ref> <ref>PMID:16751771</ref> <ref>PMID:31370103</ref> <ref>PMID:40725001</ref> <ref>PMID:9845349</ref>   Lacks sodium- and chloride-dependent glycine transporter activity.<ref>PMID:10381548</ref>   Lacks sodium- and chloride-dependent glycine transporter activity.<ref>PMID:10381548</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Neuronal human glycine transporter 2 (hGlyT2) plays a critical role in maintaining glycinergic neurotransmission via the reuptake of glycine into presynaptic neurons by using the driving force of sodium and chloride ion gradients. hGlyT2 represents an important drug target for analgesic purpose. However, its structure and the molecular mechanisms remain elusive. Here, we report structures of hGlyT2 in three functional states, including the apo state, the substrate glycine-bound state, and the inhibitor-bound states. The apo state of hGlyT2 adopts an inward conformation. The substrate glycine binds at the central pocket of hGlyT2 in its occluded conformation. Both inhibitors, ORG25543 and opiranserin, bind to an allosteric site, which is vertical to the extracellular tunnel, buried under the extracellular loop 4 (EL4) and near to the transmembrane helix 1b (TM1b). These inhibitors act as wedges to prevent the inward movement of TM1b and closure of the extracellular gate. Further structural analysis reveals both global and local conformational changes associated with the ions and glycine binding and release. These structures define the mechanisms governing transport and allosteric inhibition in hGlyT2, providing a blueprint for further development of non-opioid analgesics targeting hGlyT2.

Transport and inhibition mechanisms of human glycine transporter 2.,Ji W, Yu Y, Liu Z, Su J, Wang Q, Lai M, Wu JX Nat Commun. 2026 Apr 16;17(1):5321. doi: 10.1038/s41467-026-71935-6. PMID:41991951<ref>PMID:41991951</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wc6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wu JX]]
[[Category: Yu YZ]]
[[Category: JI WM]]