View source for 7zha


==Structure of human OCT3 in complex with inhibitor decynium-22==
<StructureSection load='7zha' size='340' side='right'caption='[[7zha]], [[Resolution|resolution]] 3.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zha]] 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=7ZHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZHA 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]] 3.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JDW:1-ethyl-2-[(1-ethylquinolin-1-ium-2-yl)methyl]quinolin-1-ium'>JDW</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=7zha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zha OCA], [https://pdbe.org/7zha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zha RCSB], [https://www.ebi.ac.uk/pdbsum/7zha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zha ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S22A3_HUMAN S22A3_HUMAN] Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity).[UniProtKB:O88446]<ref>PMID:10196521</ref> <ref>PMID:10966924</ref> <ref>PMID:12538837</ref> <ref>PMID:16581093</ref> <ref>PMID:17460754</ref> <ref>PMID:20858707</ref> <ref>PMID:35307651</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 A resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.

Structural basis of organic cation transporter-3 inhibition.,Khanppnavar B, Maier J, Herborg F, Gradisch R, Lazzarin E, Luethi D, Yang JW, Qi C, Holy M, Jantsch K, Kudlacek O, Schicker K, Werge T, Gether U, Stockner T, Korkhov VM, Sitte HH Nat Commun. 2022 Nov 7;13(1):6714. doi: 10.1038/s41467-022-34284-8. PMID:36344565<ref>PMID:36344565</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zha" style="background-color:#fffaf0;"></div>

==See Also==
*[[Organic anion transporter 3D structures|Organic anion transporter 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Khanppnavar B]]
[[Category: Korkhov V]]