7p4f
From Proteopedia
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==Crystal Structure of Monoamine Oxidase B in complex with inhibitor 1== | ==Crystal Structure of Monoamine Oxidase B in complex with inhibitor 1== | ||
| - | <StructureSection load='7p4f' size='340' side='right'caption='[[7p4f]]' scene=''> | + | <StructureSection load='7p4f' size='340' side='right'caption='[[7p4f]], [[Resolution|resolution]] 2.30Å' 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=7P4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P4F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7p4f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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='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> | + | </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='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> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AOFB_HUMAN AOFB_HUMAN] Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine. | ||
| + | <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. | ||
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| + | 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 7p4f" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monoamine oxidase|Monoamine oxidase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Binda C]] | [[Category: Binda C]] | ||
[[Category: Iacovino LG]] | [[Category: Iacovino LG]] | ||
[[Category: Pisani L]] | [[Category: Pisani L]] | ||
Revision as of 13:01, 1 February 2024
Crystal Structure of Monoamine Oxidase B in complex with inhibitor 1
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