View source for 4twf


==X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) in complex with bromomemantine==
<StructureSection load='4twf' size='340' side='right'caption='[[4twf]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4twf]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Dickeya_chrysanthemi Dickeya chrysanthemi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TWF 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]] 3.901&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR7:BROMOMEMANTINE'>BR7</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=4twf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4twf OCA], [https://pdbe.org/4twf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4twf RCSB], [https://www.ebi.ac.uk/pdbsum/4twf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4twf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ELIC_DICCH ELIC_DICCH] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pentameric ligand-gated ion channels (pLGIC) catalyze the selective transfer of ions across the cell membrane in response to a specific neurotransmitter. A variety of chemically diverse molecules, including the Alzheimer's drug memantine, block ion conduction at vertebrate pLGICs by plugging the channel pore. We show that memantine has similar potency in ELIC, a prokaryotic pLGIC, when it contains an F16'S pore mutation. X-ray crystal structures, using both memantine and its derivative, Br-memantine, reveal that the ligand is localized at the extracellular entryway of the channel pore, and the pore is in a more closed conformation than wild-type ELIC in both the presence and absence of memantine. However, using voltage clamp fluorometry we observe fluorescence changes in opposite directions during channel activation and pore block, revealing an additional conformational transition not apparent from the crystal structures. These results have important implications for drugs such as memantine, which block channel pores.

The Prokaryote Ligand-Gated Ion Channel ELIC Captured in a Pore Blocker-Bound Conformation by the Alzheimer's Disease Drug Memantine.,Ulens C, Spurny R, Thompson AJ, Alqazzaz M, Debaveye S, Han L, Price K, Villalgordo JM, Tresadern G, Lynch JW, Lummis SC Structure. 2014 Sep 3. pii: S0969-2126(14)00244-5. doi:, 10.1016/j.str.2014.07.013. PMID:25199693<ref>PMID:25199693</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4twf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dickeya chrysanthemi]]
[[Category: Large Structures]]
[[Category: Alqazzaz M]]
[[Category: Debaveye S]]
[[Category: Lu H]]
[[Category: Lummis SCR]]
[[Category: Lynch JW]]
[[Category: Price K]]
[[Category: Spurny R]]
[[Category: Thompson AJ]]
[[Category: Tresadern G]]
[[Category: Ulens C]]
[[Category: Villalgordo JM]]