View source for 5xgl


==Co-crystal structure of Ac-AChBPP in complex with alpha-conotoxin LvIA==
<StructureSection load='5xgl' size='340' side='right'caption='[[5xgl]], [[Resolution|resolution]] 3.44&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xgl]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica] and [https://en.wikipedia.org/wiki/Conus_lividus Conus lividus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XGL 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]] 3.439&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=5xgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xgl OCA], [https://pdbe.org/5xgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xgl RCSB], [https://www.ebi.ac.uk/pdbsum/5xgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xgl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The alpha3* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The alpha-conotoxin (alpha-CTx) LvIA has been identified as the most selective inhibitor of alpha3beta2 nAChRs known to date, and it can distinguish the alpha3beta2 nAChR subtype from the alpha6/alpha3beta2beta3 and alpha3beta4 nAChR subtypes. However, the mechanism of its selectivity towards alpha3beta2, alpha6/alpha3beta2beta3, and alpha3beta4 nAChRs remains elusive. Here we report the co-crystal structure of LvIA in complex with Aplysia californica acetylcholine binding protein (Ac-AChBP) at a resolution of 3.4 A. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvIA plays an important role in the selectivity of LvIA towards alpha3beta2 and alpha3/alpha6beta2beta3 nAChRs by making a salt bridge with Lys-155 of the rat alpha3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat beta2 subunit in the alpha3beta2 nAChR model, revealing the reason for its more potent selectivity towards the alpha3beta2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target alpha3beta2 nAChRs, with significant implications for the design of new therapeutic alpha-CTxs.

The crystal structure of Ac-AChBP in complex with alpha-conotoxin LvIA reveals the mechanism of its selectivity towards different nAChR subtypes.,Xu M, Zhu X, Yu J, Yu J, Luo S, Wang X Protein Cell. 2017 Sep;8(9):675-685. doi: 10.1007/s13238-017-0426-2. Epub 2017, Jun 5. PMID:28585176<ref>PMID:28585176</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xgl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aplysia californica]]
[[Category: Conus lividus]]
[[Category: Large Structures]]
[[Category: Luo SL]]
[[Category: Wang XQ]]
[[Category: Xu MY]]
[[Category: Zhu XP]]