7qb4

Mus Musculus Acetylcholinesterase in complex with 7-[(1-benzylpiperidin-3-yl)methoxy]-3,4-dimethyl-2H-chromen-2-one

spinqualitylabelsall models 7qb4, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.500011Å Ligands: 9YU, AJ9, EDO, NAG, PG0, TOE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Multitarget directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies. The synergistic inhibition of monoamine oxidase B (MAO B) and acetylcholinesterase (AChE) is believed to provide a potentiated effect in the treatment of Alzheimer's disease. Among previously reported micromolar or sub-micromolar coumarin-bearing dual inhibitors, compound 1 returned a tight-binding inhibition of MAO B (K i = 4.5 muM) and a +5.5 degrees C increase in the enzyme T m value. Indeed, the X-ray crystal structure revealed that binding of 1 produces unforeseen conformational changes at the MAO B entrance cavity. Interestingly, 1 showed great shape complementarity with the AChE enzymatic gorge, being deeply buried from the catalytic anionic subsite (CAS) to the peripheral anionic subsite (PAS) and causing significant structural changes in the active site. These findings provide structural templates for further development of dual MAO B and AChE inhibitors. Dual Reversible Coumarin Inhibitors Mutually Bound to Monoamine Oxidase B and Acetylcholinesterase Crystal Structures.,Ekstrom F, Gottinger A, Forsgren N, Catto M, Iacovino LG, Pisani L, Binda C ACS Med Chem Lett. 2022 Feb 18;13(3):499-506. doi:, 10.1021/acsmedchemlett.2c00001. eCollection 2022 Mar 10. PMID:35300078 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

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