3U8K
Crystal structure of the acetylcholine binding protein (AChBP) from Lymnaea stagnalis in complex with NS3573 (1-(5-ethoxypyridin-3-yl)-1,4-diazepane)
Summary for 3U8K
| Entry DOI | 10.2210/pdb3u8k/pdb |
| Related | 1UV6 1UW6 3U8J 3U8L 3U8M 3U8N |
| Descriptor | Acetylcholine-binding protein, 1-(5-ethoxypyridin-3-yl)-1,4-diazepane, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | lymnaea stagnalis, agonist, ligand-bindig domain, acetylcholine, acetylcholine-binding protein, acetylcholine-binding protein-agonist complex, acetylcholine-binding protein/agonist |
| Biological source | Lymnaea stagnalis (Great pond snail) |
| Cellular location | Secreted: P58154 |
| Total number of polymer chains | 20 |
| Total formula weight | 483300.69 |
| Authors | Rohde, L.A.H.,Ahring, P.K.,Jensen, M.L.,Nielsen, E.O.,Peters, D.,Helgstrand, C.,Krintel, C.,Harpsoe, K.,Gajhede, M.,Kastrup, J.S.,Balle, T. (deposition date: 2011-10-17, release date: 2011-12-14, Last modification date: 2024-10-16) |
| Primary citation | Rohde, L.A.,Ahring, P.K.,Jensen, M.L.,Nielsen, E.,Peters, D.,Helgstrand, C.,Krintel, C.,Harpse, K.,Gajhede, M.,Kastrup, J.S.,Balle, T. Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine alpha 4 beta 2 receptors: unique role of halogen bonding revealed. J.Biol.Chem., 287:4248-4259, 2012 Cited by PubMed Abstract: The α4β2 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 α4β2 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 α4β2 and the acetylcholine-binding protein from Lymnaea stagnalis (Ls-AChBP) confirms Ls-AChBP as structural surrogate for α4β2 receptors. Crystal structures of five agonists with efficacies at α4β2 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. PubMed: 22170047DOI: 10.1074/jbc.M111.292243 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.47 Å) |
Structure validation
Download full validation report
