An unusual pattern of ligand-receptor interactions for the α7 nicotinic acetylcholine receptor, with implications for the binding of varenicline

Molecular Pharmacology

Volumn 84, Issue 2, 2013, Pages 201-207

  Van Arnam, Ethan B ^a   Blythe, Emily E ^a   Lester, Henry A ^b   Dougherty, Dennis A ^a  

^a California Institute of Technology   (United States)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; AMINO ACID; BUNGAROTOXIN RECEPTOR; CATION; EPIBATIDINE; LIGAND RECEPTOR; PROTEIN; RECEPTOR; TRPB PROTEIN; UNCLASSIFIED DRUG; VARENICLINE;

ARTICLE; BINDING SITE; CONTROLLED STUDY; DRUG PROTEIN BINDING; HYDROGEN BOND; MUTAGENESIS; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RAT;

ACETYLCHOLINE; ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR; ANIMALS; BENZAZEPINES; BICYCLO COMPOUNDS, HETEROCYCLIC; BINDING SITES; HUMANS; HYDROGEN BONDING; LIGANDS; MODELS, MOLECULAR; NICOTINIC AGONISTS; OOCYTES; PYRIDINES; QUINOXALINES; RATS; XENOPUS LAEVIS;

EID: 84880595979     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.113.085795     Document Type: Article

References (40)

1. Beene DL, Brandt GS, Zhong W, Zacharias NM, Lester HA, and Dougherty DA (2002) Cation-pi interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. Biochemistry 41:10262-10269.
2. Beers WH and Reich E (1970) Structure and activity of acetylcholine. Nature 228: 917-922.
3. Billen B, Spurny R, Brams M, van Elk R, Valera-Kummer S, Yakel JL, Voets T, Bertrand D, Smit AB, and Ulens C (2012) Molecular actions of smoking cessation drugs at α4β2 nicotinic receptors defined in crystal structures of a homologous binding protein. Proc Natl Acad Sci USA 109:9173-9178.
4. Blum AP, Lester HA, and Dougherty DA (2010) Nicotinic pharmacophore: the pyridine N of nicotine and carbonyl of acetylcholine hydrogen bond across a subunit interface to a backbone NH. Proc Natl Acad Sci USA 107:13206-13211.
5. Blum AP, Van Arnam EB, German LA, Lester HA, and Dougherty DA (2013) Binding interactions with the complementary subunit of nicotinic receptors. J Biol Chem 288:6991-6997.
6. Cashin AL, Petersson EJ, Lester HA, and Dougherty DA (2005) Using physical chemistry to differentiate nicotinic from cholinergic agonists at the nicotinic acetylcholine receptor. J Am Chem Soc 127:350-356.
7. Celie PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, and Sixma TK (2004) Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41:907-914.
8. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, and Fox CB et al. (2005) Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 48:3474-3477.
9. de Jonge WJ and Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151:915-929.
10. Dougherty DA (2008) Cys-loop neuroreceptors: structure to the rescue? Chem Rev 108:1642-1653.
11. England PM, Lester HA, and Dougherty DA (1999) Incorporation of esters into proteins: Improved synthesis of hydroxyacyl tRNAs. Tetrahedron Lett 40: 6189-6192.
12. Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, and Bourne Y (2005) Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations. EMBO J 24:3635-3646.
13. Hernandez CM and Dineley KT (2012) α7 Nicotinic acetylcholine receptors in Alzheimer's disease: neuroprotective, neurotrophic or both? Curr Drug Targets 13: 613-622.
14. Horenstein NA, Leonik FM, and Papke RL (2008) Multiple pharmacophores for the selective activation of nicotinic alpha7-type acetylcholine receptors. Mol Pharmacol 74:1496-1511.
15. Le Novère N, Corringer PJ, and Changeux JP (2002) The diversity of subunit composition in nAChRs: evolutionary origins, physiologic and pharmacologic consequences. J Neurobiol 53:447-456.
16. Li SX, Huang S, Bren N, Noridomi K, Dellisanti CD, Sine SM, and Chen L (2011) Ligand-binding domain of an α7-nicotinic receptor chimera and its complex with agonist. Nat Neurosci 14:1253-1259.
17. Lummis SC, L Beene D, Harrison NJ, Lester HA, and Dougherty DA (2005) A cationpi binding interaction with a tyrosine in the binding site of the GABAC receptor. Chem Biol 12:993-997.
18. Martin LF, Kem WR, and Freedman R (2004) Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl) 174:54-64.
19. Mazurov AA, Speake JD, and Yohannes D (2011) Discovery and development of α7 nicotinic acetylcholine receptor modulators. J Med Chem 54:7943-7961.
20. Mihalak KB, Carroll FI, and Luetje CW (2006) Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 70:801-805.
21. Nemecz A and Taylor P (2011) Creating an α7 nicotinic acetylcholine recognition domain from the acetylcholine-binding protein: crystallographic and ligand selectivity analyses. J Biol Chem 286:42555-42565.
22. Nowak MW, Gallivan JP, Silverman SK, Labarca CG, Dougherty DA, and Lester HA (1998) In vivo incorporation of unnatural amino acids into ion channels in Xenopus oocyte expression system. Methods Enzymol 293:504-529.
23. Papke RL, Bencherif M, and Lippiello P (1996) An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the alpha 7 subtype. Neurosci Lett 213:201-204.
24. Papke RL, Stokes C, Williams DK, Wang J, and Horenstein NA (2011a) Cysteine accessibility analysis of the human alpha7 nicotinic acetylcholine receptor ligand-binding domain identifies L119 as a gatekeeper. Neuropharmacology 60: 159-171.
25. Papke RL, Trocmé-Thibierge C, Guendisch D, Al Rubaiy SA, and Bloom SA (2011b) Electrophysiological perspectives on the therapeutic use of nicotinic acetylcholine receptor partial agonists. J Pharmacol Exp Ther 337:367-379.
26. Placzek AN, Grassi F, Meyer EM, and Papke RL (2005) An alpha7 nicotinic acetylcholine receptor gain-of-function mutant that retains pharmacological fidelity. Mol Pharmacol 68:1863-1876.
27. Pless SA, Millen KS, Hanek AP, Lynch JW, Lester HA, Lummis SC, and Dougherty DA (2008) A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. J Neurosci 28:10937-10942.
28. Puskar NL, Xiu X, Lester HA, and Dougherty DA (2011) Two neuronal nicotinic acetylcholine receptors, alpha4beta4 and alpha7, show differential agonist binding modes. J Biol Chem 286:14618-14627.
29. Rodriguez EA, Lester HA, and Dougherty DA (2007a) Improved amber and opal suppressor tRNAs for incorporation of unnatural amino acids in vivo. Part 1: minimizing misacylation. RNA 13:1703-1714.
30. Rodriguez EA, Lester HA, and Dougherty DA (2007b) Improved amber and opal suppressor tRNAs for incorporation of unnatural amino acids in vivo. Part 2: evaluating suppression efficiency. RNA 13:1715-1722.
31. Rohde LA, Ahring PK, Jensen ML, Nielsen EO, Peters D, Helgstrand C, Krintel C, Harpsøe K, Gajhede M, and Kastrup JS et al. (2012) Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine α4β2 receptors: unique role of halogen bonding revealed. J Biol Chem 287:4248-4259.
32. Rucktooa P, Haseler CA, van Elk R, Smit AB, Gallagher T, and Sixma TK (2012) Structural characterization of binding mode of smoking cessation drugs to nicotinic acetylcholine receptors through study of ligand complexes with acetylcholinebinding protein. J Biol Chem 287:23283-23293.
33. Rucktooa P, Smit AB, and Sixma TK (2009) Insight in nAChR subtype selectivity from AChBP crystal structures. Biochem Pharmacol 78:777-787.
34. Saks ME, Sampson JR, Nowak MW, Kearney PC, Du F, Abelson JN, Lester HA, and Dougherty DA (1996) An engineered Tetrahymena tRNAGln for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression. J Biol Chem 271:23169-23175.
35. Sixma TK and Smit AB (2003) Acetylcholine binding protein (AChBP): a secreted glial protein that provides a high-resolution model for the extracellular domain of pentameric ligand-gated ion channels. Annu Rev Biophys Biomol Struct 32: 311-334.
36. Tavares XdaS, Blum AP, Nakamura DT, Puskar NL, Shanata JA, Lester HA, and Dougherty DA (2012) Variations in binding among several agonists at two stoichiometries of the neuronal, α4β2 nicotinic receptor. J Am Chem Soc 134: 11474-11480.
37. Talley TT, Harel M, Hibbs RE, Radic Z, Tomizawa M, Casida JE, and Taylor P (2008) Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophore. Proc Natl Acad Sci USA 105: 7606-7611.
38. Thorson JS, Chapman E, Murphy EC, Schultz PG, and Judice JK (1995) Linear freeenergy analysis of hydrogen-bonding in proteins. J Am Chem Soc 117:1157-1158.
39. Xiu X, Puskar NL, Shanata JA, Lester HA, and Dougherty DA (2009) Nicotine binding to brain receptors requires a strong cation-pi interaction. Nature 458: 534-537.
40. Zhong W, Gallivan JP, Zhang Y, Li L, Lester HA, and Dougherty DA (1998) From ab initio quantum mechanics to molecular neurobiology: a cation-pi binding site in the nicotinic receptor. Proc Natl Acad Sci USA 95:12088-12093. Disorders and Stroke