3u8j | pdb_00003u8j

Crystal structure of the acetylcholine binding protein (AChBP) from Lymnaea stagnalis in complex with NS3531 (1-(pyridin-3-yl)-1,4-diazepane)

spinqualitylabelsall models 3u8j, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u8j is a 10 chain structure with sequence from Lymnaea stagnalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: 09O, NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACHP_LYMST Binds to acetylcholine. Modulates neuronal synaptic transmission. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholine binding protein 3D structures

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