View source for 3gwu


==Leucine transporter LeuT in complex with sertraline==
<StructureSection load='3gwu' size='340' side='right'caption='[[3gwu]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gwu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GWU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LEU:LEUCINE'>LEU</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SRE:(1S,4S)-4-(3,4-DICHLOROPHENYL)-N-METHYL-1,2,3,4-TETRAHYDRONAPHTHALEN-1-AMINE'>SRE</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=3gwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gwu OCA], [https://pdbe.org/3gwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gwu RCSB], [https://www.ebi.ac.uk/pdbsum/3gwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gwu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O67854_AQUAE O67854_AQUAE] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gw/3gwu_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gwu ConSurf].
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== Publication Abstract from PubMed ==
Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.,Zhou Z, Zhen J, Karpowich NK, Law CJ, Reith ME, Wang DN Nat Struct Mol Biol. 2009 Jun;16(6):652-7. Epub 2009 May 10. PMID:19430461<ref>PMID:19430461</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3gwu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Leucine transporter|Leucine transporter]]
*[[Serotonin Transporter|Serotonin Transporter]]
*[[Symporter 3D structures|Symporter 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus VF5]]
[[Category: Large Structures]]
[[Category: Karpowich NK]]
[[Category: Law CJ]]
[[Category: Reith MEA]]
[[Category: Wang DN]]
[[Category: Zhen J]]
[[Category: Zhou Z]]