6g1w

Crystal structure of Torpedo Californica acetylcholinesterase in complex with 2-{1-[2-(6-Chloro-1,2,3,4-tetrahydroacridin-9-ylamino)ethyl]-1H-1,2,3-triazol-4-yl}-N-[4-(hydroxy)-3-methoxybenzyl]acetamide

spinqualitylabelsall models 6g1w, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6g1w is a 2 chain structure with sequence from Tetronarce californica. This structure supersedes the now removed PDB entry 6fov. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, E0Z, NAG Activity: Acetylcholinesterase, with EC number 3.1.1.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ACES_TETCF] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. Publication Abstract from PubMed Symptomatic treatment of myasthenia gravis is based on the use of peripherally-acting acetylcholinesterase (AChE) inhibitors that, in some cases, must be discontinued due to the occurrence of a number of side-effects. Thus, new AChE inhibitors are being developed and investigated for their potential use against this disease. Here, we have explored two alternative approaches to get access to peripherally-acting AChE inhibitors as new agents against myasthenia gravis, by structural modification of the brain permeable anti-Alzheimer AChE inhibitors tacrine, 6-chlorotacrine, and huprine Y. Both quaternization upon methylation of the quinoline nitrogen atom, and tethering of a triazole ring, with, in some cases, the additional incorporation of a polyphenol-like moiety, result in more polar compounds with higher inhibitory activity against human AChE (up to 190-fold) and butyrylcholinesterase (up to 40-fold) than pyridostigmine, the standard drug for symptomatic treatment of myasthenia gravis. The novel compounds are furthermore devoid of brain permeability, thereby emerging as interesting leads against myasthenia gravis. Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis.,Galdeano C, Coquelle N, Cieslikiewicz-Bouet M, Bartolini M, Perez B, Clos MV, Silman I, Jean L, Colletier JP, Renard PY, Munoz-Torrero D Molecules. 2018 Mar 11;23(3). pii: molecules23030634. doi:, 10.3390/molecules23030634. PMID:29534488 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

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