7p4f: Difference between revisions
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<StructureSection load='7p4f' size='340' side='right'caption='[[7p4f]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='7p4f' size='340' side='right'caption='[[7p4f]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P4F FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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]] 2.3Å</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=C15:N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE'>C15</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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=C15:N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE'>C15</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=7p4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p4f OCA], [https://pdbe.org/7p4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p4f RCSB], [https://www.ebi.ac.uk/pdbsum/7p4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p4f ProSAT]</span></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=7p4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p4f OCA], [https://pdbe.org/7p4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p4f RCSB], [https://www.ebi.ac.uk/pdbsum/7p4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p4f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Binda C]] | [[Category: Binda C]] | ||
[[Category: Iacovino LG]] | [[Category: Iacovino LG]] | ||
[[Category: Pisani L]] | [[Category: Pisani L]] | ||
Latest revision as of 14:18, 23 October 2024
Crystal Structure of Monoamine Oxidase B in complex with inhibitor 1Crystal Structure of Monoamine Oxidase B in complex with inhibitor 1
Structural highlights
Publication Abstract from PubMedMultitarget 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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