4AFT

Aplysia californica AChBP in complex with Varenicline

Summary for 4AFT

• Entry DOI: 10.2210/pdb4aft/pdb
• Related: 2BR7 2BR8 2BYN 2BYP 2BYQ 2BYR 2BYS 2C9T 2UZ6 2W8F 2W8G 2WN9 2WNC 2WNJ 2WNL 2WZY 2X00 2XNT 2XNU 2XNV 2XYS 2XYT 2XZ5 2XZ6 2Y54 2Y56 2Y57 2Y58 2Y7Y 4AFO 4AFW
• Descriptor: SOLUBLE ACETYLCHOLINE RECEPTOR, VARENICLINE (2 entities in total)
• Functional Keywords: receptor protein, nicotinic
• Biological source: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE)
• Total number of polymer chains: 5
• Total formula weight: 124499.20

Authors

Rucktooa, P.,Haseler, C.A.,vanElke, R.,Smit, A.B.,Gallagher, T.,Sixma, T.K. (deposition date: 2012-01-23, release date: 2012-05-02, Last modification date: 2024-11-13)

Primary citation

Rucktooa, P.,Haseler, C.A.,Van Elk, R.,Smit, A.B.,Gallagher, T.,Sixma, T.K.
Structural Characterization of Binding Mode of Smoking Cessation Drugs to Nicotinic Acetylcholine Receptors Through Study of Ligand Complexes with Acetylcholine-Binding Protein.
J.Biol.Chem., 287:23283-, 2012

PubMed Abstract: Smoking cessation is an important aim in public health worldwide as tobacco smoking causes many preventable deaths. Addiction to tobacco smoking results from the binding of nicotine to nicotinic acetylcholine receptors (nAChRs) in the brain, in particular the α4β2 receptor. One way to aid smoking cessation is by the use of nicotine replacement therapies or partial nAChR agonists like cytisine or varenicline. Here we present the co-crystal structures of cytisine and varenicline in complex with Aplysia californica acetylcholine-binding protein and use these as models to investigate binding of these ligands binding to nAChRs. This analysis of the binding properties of these two partial agonists provides insight into differences with nicotine binding to nAChRs. A mutational analysis reveals that the residues conveying subtype selectivity in nAChRs reside on the binding site complementary face and include features extending beyond the first shell of contacting residues.

PubMed: 22553201
DOI: 10.1074/JBC.M112.360347

Experimental method

X-RAY DIFFRACTION (3.2 Å)