View source for 2lkh


==WSA minor conformation==
<StructureSection load='2lkh' size='340' side='right'caption='[[2lkh]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2lkh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Torpedo_marmorata Torpedo marmorata]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LKH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2lkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkh OCA], [https://pdbe.org/2lkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lkh RCSB], [https://www.ebi.ac.uk/pdbsum/2lkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lkh ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The nicotinic acetylcholine receptor (nAChR) is an important therapeutic target for a wide range of pathophysiological conditions, for which rational drug designs often require receptor structures at atomic resolution. Recent proof-of-concept studies demonstrated a water-solubilization approach to structure determination of membrane proteins by NMR (Slovic et al., PNAS, 101: 1828-1833, 2004; Ma et al., PNAS, 105: 16537-42, 2008). We report here the computational design and experimental characterization of WSA, a water-soluble protein with ~83% sequence identity to the transmembrane (TM) domain of the nAChR alpha1 subunit. Although the design was based on a low-resolution structural template, the resulting high-resolution NMR structure agrees remarkably well with the recent crystal structure of the TM domains of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel (GLIC), demonstrating the robustness and general applicability of the approach. NMR T(2) dispersion measurements showed that the TM2 domain of the designed protein was dynamic, undergoing conformational exchange on the NMR timescale. Photoaffinity labeling with isoflurane and propofol photolabels identified a common binding site in the immediate proximity of the anesthetic binding site found in the crystal structure of the anesthetic-GLIC complex. Our results illustrate the usefulness of high-resolution NMR analyses of water-solubilized channel proteins for the discovery of potential drug binding sites.

NMR structure and dynamics of water-solubilized transmembrane domains of nicotinic acetylcholine receptor.,Cui T, Mowrey D, Bondarenko V, Tillman T, Ma D, Landrum E, Perez-Aguilar JM, He J, Wang W, Saven JG, Eckenhoff R, Tang P, Xu Y Biochim Biophys Acta. 2011 Dec 3. PMID:22155685<ref>PMID:22155685</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 2lkh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Torpedo marmorata]]
[[Category: Cui T]]
[[Category: Eckenhoff R]]
[[Category: Mowrey D]]
[[Category: Perez-Aguilar J]]
[[Category: Saven JG]]
[[Category: Tang P]]
[[Category: Xu Y]]