Nicotinic acetylcholine receptor molecular models

The primary sequences of important channel peptides, such as the nicotinic acetylcholine receptors, and sodium, potassium, and calcium channels, have been determined by the innovative work of the late professor Numa and his group. " Thereafter, various structural models on the basis of empirical as well as molecular mechanics or molecular dynamics calculations were proposed " and tested by specific point mutation studies. 

The modes of action of different alkaloids are diverse. For example, nicotine binds to and affects nicotinic acetylcholine receptors and shows toxicity. A recent molecular 3D model suggests that both acetylcholine and nicotine bind to the same pocket formed in a nicotinic acetylcholine receptor.15 Morphine binds to and activates opioid receptors, transmembrane-spanning G protein-coupled receptors, in the central nervous system of humans.16 Caffeine, which is structurally similar to adenine, inhibits cyclic AMP phosphodiesterase activity and inhibits the degradation of cAMP, thus exerting a toxic effect on insects 17 in human beings, binding of caffeine to the adenosine A2A receptor induces wakefulness.18 Atropine binds to muscarinic acetylcholine receptors, competing with acetylcholine, and blocks neurotransmission.1... 

Klaassen A, Glykys J, Maguire J, Labarca C, Mody I, Boulter J (2006) Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy. Proc Natl Acad Sci USA 10350 19152-19157 Klink R, de Kerchove dA, Zoh M, Changeux JP (2001) Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci 21 1452-1463... 

Keywords Nicotinic acetylcholine receptor (nAChR) oic4p2 Nicotine Epibatidine Pyrrolizidine 2-azabicyclo[2.2.1 Jheptane Furo[2,3-h]pyridine Furo[3,2-b]pyridine Pharmacophore Pyridyl ether Furo[2,3-c]pyridine Furo[3,2-c]pyridine Molecular modelling... 

T0nder JE, Olesen PH (2001) Agonists at the a4P2 nicotinic acetylcholine receptors structure-activity relationships and molecular modelling. Curr Med Chem 8 651-674... 

Paramagnetic relaxation enhancement (PRE) is used approach for determining long-range distance constraints in biomolecular solution NMR spectroscopy. Maltsev et al. showed that P PRE solid-state NMR spectroscopy can be utilized to determine the immersion depth of spin-labeled membrane peptides and proteins. Changes in the P NMR PRE times coupled with modelling studies can be used to describe the spin-label position/amino acid within the lipid bilayer and the corresponding helical tilt and the alpha-helical nicotinic acetylcholine receptor nAChR M2 delta transmembrane is used to show this. This PRE ssNMR technique can be used as a molecular ruler to measure membrane immersion depth. ... 

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