7qak
From Proteopedia
(Difference between revisions)
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==Mus Musculus Acetylcholinesterase in complex with 7-[(4-{[benzyl(methyl)amino]methyl}benzyl)oxy]-4-(hydroxymethyl)-2H-chromen-2-one== | ==Mus Musculus Acetylcholinesterase in complex with 7-[(4-{[benzyl(methyl)amino]methyl}benzyl)oxy]-4-(hydroxymethyl)-2H-chromen-2-one== | ||
| - | <StructureSection load='7qak' size='340' side='right'caption='[[7qak]]' scene=''> | + | <StructureSection load='7qak' size='340' side='right'caption='[[7qak]], [[Resolution|resolution]] 2.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7qak]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAK FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qak OCA], [https://pdbe.org/7qak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qak RCSB], [https://www.ebi.ac.uk/pdbsum/7qak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qak ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6000032Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5IK:4-(hydroxymethyl)-7-[[4-[[methyl-(phenylmethyl)amino]methyl]phenyl]methoxy]chromen-2-one'>5IK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P15:2,5,8,11,14,17-HEXAOXANONADECAN-19-OL'>P15</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qak OCA], [https://pdbe.org/7qak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qak RCSB], [https://www.ebi.ac.uk/pdbsum/7qak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qak ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ACES_MOUSE ACES_MOUSE] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:35300078</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7qak" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
[[Category: Ekstrom FJ]] | [[Category: Ekstrom FJ]] | ||
[[Category: Forsgren N]] | [[Category: Forsgren N]] | ||
Revision as of 13:15, 1 February 2024
Mus Musculus Acetylcholinesterase in complex with 7-[(4-{[benzyl(methyl)amino]methyl}benzyl)oxy]-4-(hydroxymethyl)-2H-chromen-2-one
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