Related ArticlesProbing the agonist binding pocket in the nicotinic acetylcholine receptor: a high-resolution solid-state NMR approach.
Biochemistry. 1998 Jul 28;37(30):10854-9
Authors: Williamson PT, Gröbner G, Spooner PJ, Miller KW, Watts A
Acetylcholine, the agonist for the nicotinic acetylcholine receptor, has been observed directly when bound specifically to its binding site in the fully functional receptor-enriched membranes from Torpedo nobiliana. High-resolution solid-state, magic angle spinning 13C NMR methods have been used to observe selectively N+(13CH3)3 acetylcholine bound in as few as 20 nmol of receptor binding sites, against a background of natural abundance membrane resonances and excess acetylcholine in free solution. The specificity of the binding has been demonstrated to be pharmacologically significant through the use of the competitive inhibitor alpha bungarotoxin which selectively displaces and prevents binding of acetylcholine to the membrane-bound receptor. The chemical shift assigned to N+(13CH3)3 acetylcholine in solution and crystalline solid is 53.9 +/- 0.04 ppm, and it changes by 1.6 ppm (p < 0.05) for agonist when bound specifically in the receptor binding site. Through the use of computer simulations of chemical shifts carried out on acetylcholine bound to the acetylcholinesterase, we propose that the cause for this change is the presence of aromatic side chains lining the receptor binding site. It is suggested that the binding of acetylcholine to the nicotinic acetylcholine receptor is mediated primarily through the interaction of the quaternary ammonium group of the acetylcholine with the pi bonded systems in the aromatic side chains. Longitudinal relaxation time measurements show that the residency time for the acetylcholine observed in DDCP experiments is long (> 200 ms) with respect to the longitudinal relaxation time of other assignable resonances within the spectrum from the lipid and protein and confirms that the acetylcholine is protein-associated, and not free in solution or nonspecifically bound.
Nmr structure and action on nicotinic acetylcholine receptors of water-soluble domain of human lynx1.
NMR STRUCTURE AND ACTION ON NICOTINIC ACETYLCHOLINE RECEPTORS OF WATER-SOLUBLE DOMAIN OF HUMAN LYNX1.
NMR STRUCTURE AND ACTION ON NICOTINIC ACETYLCHOLINE RECEPTORS OF WATER-SOLUBLE DOMAIN OF HUMAN LYNX1.
J Biol Chem. 2011 Jan 20;
Authors: Lyukmanova EN, Shenkarev ZO, Shulepko MA, Mineev KS, D'Hoedt D, Kasheverov IE, Filkin SY, Krivolapova AP, Janickova H, Dolezal V, Dolgikh DA, Arseniev AS, Bertrand D, Tsetlin VI, Kirpichnikov MP
Discovery of proteins expressed in the central nervous system sharing the three-finger structure with snake...
[NMR paper] NMR structure of the thromboxane A2 receptor ligand recognition pocket.
NMR structure of the thromboxane A2 receptor ligand recognition pocket.
Related Articles NMR structure of the thromboxane A2 receptor ligand recognition pocket.
Eur J Biochem. 2004 Jul;271(14):3006-16
Authors: Ruan KH, Wu J, So SP, Jenkins LA, Ruan CH
To overcome the difficulty of characterizing the structures of the extracellular loops (eLPs) of G protein-coupled receptors (GPCRs) other than rhodopsin, we have explored a strategy to generate a three-dimensional structural model for a GPCR, the thromboxane A(2) receptor. This three-dimensional...
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[NMR paper] Towards structure determination of neurotoxin II bound to nicotinic acetylcholine rec
Towards structure determination of neurotoxin II bound to nicotinic acetylcholine receptor: a solid-state NMR approach.
Related Articles Towards structure determination of neurotoxin II bound to nicotinic acetylcholine receptor: a solid-state NMR approach.
FEBS Lett. 2004 Apr 30;564(3):319-24
Authors: Krabben L, van Rossum BJ, Castellani F, Bocharov E, Schulga AA, Arseniev AS, Weise C, Hucho F, Oschkinat H
Solid-state magic-angle spinning nuclear magnetic resonance (NMR) has sufficient resolving power for full assignment of resonances and...
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[NMR paper] Refinement of the geometry of the retinal binding pocket in dark-adapted bacteriorhod
Refinement of the geometry of the retinal binding pocket in dark-adapted bacteriorhodopsin by heteronuclear solid-state NMR distance measurements.
Related Articles Refinement of the geometry of the retinal binding pocket in dark-adapted bacteriorhodopsin by heteronuclear solid-state NMR distance measurements.
Biochemistry. 2000 Aug 22;39(33):10066-71
Authors: Helmle M, Patzelt H, Ockenfels A, Gärtner W, Oesterhelt D, Bechinger B
The bacterial proton pump bacteriorhodopsin (BR) is a 26.5 kDa seven-transmembrane helical protein. Several...
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[NMR paper] NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors.
NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors.
Related Articles NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors.
Biophys J. 2000 Feb;78(2):746-51
Authors: Xu Y, Seto T, Tang P, Firestone L
New lines of evidence suggest that volatile anesthetics interact specifically with proteins. Direct binding analysis, however, has been largely limited to soluble proteins. In this study, specific interaction was investigated between isoflurane, a clinically important volatile anesthetic, and...
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[NMR paper] Evaluation of Solvent Accessibility to the [Fe(4)S(4)] Binding Pocket in Native and T
Evaluation of Solvent Accessibility to the Binding Pocket in Native and Tyr19 Mutant High Potential Iron Proteins by (1)H-(15)N HMQC and (19)F NMR Experiments.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles Evaluation of Solvent Accessibility to the Binding Pocket in Native and Tyr19 Mutant High Potential Iron Proteins by (1)H-(15)N HMQC and (19)F NMR Experiments.
Inorg Chem. 1996 Feb 28;35(5):1121-1125
Authors: Li D, Agarwal A, Cowan JA
The solvent accessibility of Chromatium...
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[NMR paper] Direct measurement of agonist binding to genetically engineered peptides of the acety
Direct measurement of agonist binding to genetically engineered peptides of the acetylcholine receptor by selective T1 NMR relaxation.
Related Articles Direct measurement of agonist binding to genetically engineered peptides of the acetylcholine receptor by selective T1 NMR relaxation.
Biochemistry. 1990 Mar 13;29(10):2617-22
Authors: Fraenkel Y, Navon G, Aronheim A, Gershoni JM
Interactions of four ligands of the nicotinic acetylcholine receptor with genetically engineered peptides have been studied by NMR. A recombinant cholinergic binding...