8xb4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of apo state of the human Norepinephrine Transporter== | |
| + | <StructureSection load='8xb4' size='340' side='right'caption='[[8xb4]], [[Resolution|resolution]] 2.92Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8xb4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XB4 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]] 2.92Å</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=8xb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xb4 OCA], [https://pdbe.org/8xb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xb4 RCSB], [https://www.ebi.ac.uk/pdbsum/8xb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xb4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/SC6A2_HUMAN SC6A2_HUMAN] Postural orthostatic tachycardia syndrome due to NET deficiency. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SC6A2_HUMAN SC6A2_HUMAN] Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921).<ref>PMID:11093780</ref> <ref>PMID:2008212</ref> <ref>PMID:8125921</ref> [https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level(1). Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target(1). However, the structure and mechanism of NET remain unclear. Here we provide cryogenic electron microscopy structures of the human NET (hNET) in three functional states-the apo state, and in states bound to the substrate meta-iodobenzylguanidine (MIBG) or the orthosteric inhibitor radafaxine. These structures were captured in an inward-facing conformation, with a tightly sealed extracellular gate and an open intracellular gate. The substrate MIBG binds at the centre of hNET. Radafaxine also occupies the substrate-binding site and might block the structural transition of hNET for inhibition. These structures provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET. | ||
| - | + | Substrate binding and inhibition mechanism of norepinephrine transporter.,Ji W, Miao A, Liang K, Liu J, Qi Y, Zhou Y, Duan X, Sun J, Lai L, Wu JX Nature. 2024 Aug 14. doi: 10.1038/s41586-024-07810-5. PMID:39143211<ref>PMID:39143211</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8xb4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli K-12]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ji WM]] | ||
| + | [[Category: Wu JX]] | ||
Current revision
Structure of apo state of the human Norepinephrine Transporter
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