Neuromodulators
From Proteopedia
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Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine, nitric oxide, and several neuropeptides. Cannabinoids can also be powerful CNS neuromodulators. | Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine, nitric oxide, and several neuropeptides. Cannabinoids can also be powerful CNS neuromodulators. | ||
| + | =Acetylcholine= | ||
| + | [http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase] ([http://www.expasy.org/enzyme/3.1.1.7 EC 3.1.1.7], ''e.g.'' from [http://en.wikipedia.org/wiki/Pacific_electric_ray ''Torpedo californica''], ''Tc''AChE) [http://en.wikipedia.org/wiki/Hydrolysis hydrolysizes] the [http://en.wikipedia.org/wiki/Neurotransmitter neurotransmitter] [http://en.wikipedia.org/wiki/Acetylcholine acetylcholine] <scene name='2ace/Cv/2'>(ACh)</scene>, producing <scene name='2ace/Cv/3'>choline and an acetate</scene> group. ACh directly binds <scene name='2ace/Cv/4'>Ser200</scene> (via its [http://en.wikipedia.org/wiki/Nucleophile nucleophilic] Oγ atom) within the [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] <scene name='2ace/Cv/5'>catalytic triad (Ser200, His440, and Glu327)</scene> of (ACh/''Tc''AChE structure [[2ace]]). The residues <scene name='2ace/Cv/6'>Trp84 and Phe330</scene> are also important in the [http://en.wikipedia.org/wiki/Ligand ligand] recognition. After this binding acetylcholinesterase <scene name='2ace/Cv/7'>hydrolysizes</scene> ACh. | ||
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| + | ==Acetylcholine Receptors== | ||
| + | ===Nicotinic acetylcholine receptors=== | ||
| + | *[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptors in general]] | ||
| + | The receptor is a transmembrane pentameric glycoprotein. It cylindrical in appearance by electron microscopy approximately 16nm in length and 8nm in diameter. The main ion channel is composed of a water pore that runs through the entire length of the protein. If viewed from the synaptic cleft, the protein will look like a pseudo-symmetrical rosette shown in the picture below composed of 10 different alpha and 4 different beta subunits. | ||
| + | *<scene name='58/584302/Cv/1'>Side view</scene>. | ||
| + | *<scene name='58/584302/Cv/2'>View from extracellular side</scene>. | ||
| + | *<scene name='58/584302/Cv/3'>View from cytoplasmic side</scene>. | ||
| + | |||
| + | *[[Alpha-bungarotoxin]] is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake. | ||
| + | *[[Binding site of AChR]] | ||
| + | *[[Acetylcholine Receptor and its Reaction to Cobra Venom]] | ||
| + | When cobra venom is introduced into the body is moves along the bloodstream to a diaphragm muscle. It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. The 2nd image depicts an individual toxin binding with one chain on the receptor, both in the same color. <scene name='77/778333/Cobra_snake_venom/3'>Cobra Venom Interaction with Acetylcholine Receptor</scene>. This representation shows each molecule of the <scene name='77/778333/Venom_receptor_piece/1'>Cobra toxin binding to one chain of the receptor</scene>. | ||
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| + | ===Muscarinic acetylcholine receptors=== | ||
| + | M1, M3, M5 receptors are coupled with G<sub>q</sub> proteins, while M2 and M4 receptors are coupled with G<sub>i/o</sub> proteins. They belong to GPCRs Subfamily A18. | ||
| + | *[[Muscarinic acetylcholine receptor]] | ||
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| + | ==Acetylcholinesterase== | ||
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| + | *[[Acetylcholinesterase: Treatment of Alzheimer's disease]]<br /> | ||
| + | *[[Torpedo californica acetylcholinesterase with bifunctional inhibitor]]<br /> | ||
| + | *[[Acetylcholinesterase: Substrate Traffic and Inhibition]]<br /> | ||
| + | *[[Acetylcholinesterase Inhibitor Pharmacokinetics]]<br /> | ||
| + | *[[Acetylcholinesterase inhibitors]]<br /> | ||
| + | *[[AChE inhibitors and substrates]] <br /> | ||
| + | *[[Human Acetylcholinesterase]]<br /> | ||
| + | *[[African Malaria Mosquito Acetylcholinesterase]]<br /> | ||
| + | *[[Acetylcholinesterase inhibited by nerve agent soman]]<br /> | ||
| + | *[[Acetylcholinesterase with DFP]]<br /> | ||
| + | *[[Acetylcholinesterase with OTMA]]<br /> | ||
| + | *[[Acetylcholinesterase with acetylcholine]]<br /> | ||
| + | *[[Acetylcholinesterase complexed with N-9-(1',2',3',4'-tetrahydroacridinyl)-1,8-diaminooctane]]<br /> | ||
| + | *[[Complex of TcAChE with an iminium galanthamine derivative]]<br /> | ||
| + | *[[Complex of TcAChE with bis-acting galanthamine derivative]]<br /> | ||
| + | *[[Cholinesterase]]<br /> | ||
| + | *[[Flexibility of aromatic residues in acetylcholinesterase]]<br /> | ||
| + | *[[Huperzine A Complexed with Acetylcholinesterase]] & [[Huperzine A Complexed with Acetylcholinesterase (Chinese)]]<br /> | ||
| + | *Acetylcholinesterase complexed with [[Tacrine]], the 1st anti Alzheimer's drug<br/> | ||
| + | *[[UMass Chem 423 Student Projects 2011-1#Acetylcholinesterase bound by Tacrine|UMass Chem 423 Student Projects 2011-1: Acetylcholinesterase bound by Tacrine]] | ||
| + | *[[Torpedo Californica Acetylcholinesterase in complex with an (R)-Tacrine-(10)-Hupyridone inhibitor]]<br /> | ||
| + | *[[Torpedo Californica Acetylcholinesterase in complex with an (S)-Tacrine-(10)-Hupyridone inhibitor]]<br /> | ||
| + | *[[Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (5 carbon linker)]]<br /> | ||
| + | *[[Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (7 carbon linker)]]<br /> | ||
| + | *[[Torpedo californica acetylcholinesterase with bifunctional inhibitor]]<br /> | ||
| + | *[[Tetramerization domain of acetylcholinesterase]]<br /> | ||
| + | *[[African Malaria Mosquito Acetylcholinesterase]] | ||
| + | *[[Group:SMART:Acetylcholinesterase:A Story of Substrate Traffic and Inhibition by Green Mamba Snake Toxin]]<br /> | ||
| + | *[[Treatments:AChE Inhibitor References]]<br /> | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 12:04, 2 January 2022
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