3u8l: Difference between revisions
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New page: '''Unreleased structure''' The entry 3u8l is ON HOLD Authors: Rohde, L. A. H., Kastrup, J. S., Gajhede, M. Description: Crystal structure of the acetylcholine binding protein (AChBP) f... |
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The | ==Crystal structure of the acetylcholine binding protein (AChBP) from Lymnaea stagnalis in complex with NS3570 (1-(5-phenylpyridin-3-yl)-1,4-diazepane)== | ||
<StructureSection load='3u8l' size='340' side='right'caption='[[3u8l]], [[Resolution|resolution]] 2.32Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3u8l]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U8L 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]] 2.32Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=09Q:1-(5-PHENYLPYRIDIN-3-YL)-1,4-DIAZEPANE'>09Q</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3u8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u8l OCA], [https://pdbe.org/3u8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u8l RCSB], [https://www.ebi.ac.uk/pdbsum/3u8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u8l ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACHP_LYMST ACHP_LYMST] Binds to acetylcholine. Modulates neuronal synaptic transmission. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The alpha4beta2 subtype of the nicotinic acetylcholine receptor has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of alpha4beta2 agonists is lacking. Using binding experiments, electrophysiology and x-ray crystallography we have investigated a consecutive series of five prototypical pyridine-containing agonists derived from 1-(pyridin-3-yl)-1,4-diazepane. A correlation between binding affinities at alpha4beta2 and the acetylcholine-binding protein from Lymnaea stagnalis (Ls-AChBP) confirms Ls-AChBP as structural surrogate for alpha4beta2 receptors. Crystal structures of five agonists with efficacies at alpha4beta2 from 21-76% were determined in complex with Ls-AChBP. No variation in closure of loop C is observed despite large efficacy variations. Instead, the efficacy of a compound appears tightly coupled to its ability to form a strong intersubunit bridge linking the primary and complementary binding interfaces. For the tested agonists, a specific halogen bond was observed to play a large role in establishing such strong intersubunit anchoring. | |||
Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine alpha4beta2 receptors: unique role of halogen bonding revealed.,Rohde LA, Ahring PK, Jensen ML, Nielsen EO, Peters D, Helgstrand C, Krintel C, Harpsoe K, Gajhede M, Kastrup JS, Balle T J Biol Chem. 2012 Feb 3;287(6):4248-59. Epub 2011 Dec 13. PMID:22170047<ref>PMID:22170047</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3u8l" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lymnaea stagnalis]] | |||
[[Category: Ahring PK]] | |||
[[Category: Balle T]] | |||
[[Category: Gajhede M]] | |||
[[Category: Harpsoe K]] | |||
[[Category: Helgstrand C]] | |||
[[Category: Jensen ML]] | |||
[[Category: Kastrup JS]] | |||
[[Category: Krintel C]] | |||
[[Category: Nielsen EO]] | |||
[[Category: Peters D]] | |||
[[Category: Rohde LAH]] | |||
