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==Crystal structure of human monoamine oxidase B (MAO B) in complex with chlorophenyl-chromone-carboxamide== | ==Crystal structure of human monoamine oxidase B (MAO B) in complex with chlorophenyl-chromone-carboxamide== | ||
<StructureSection load='6fw0' size='340' side='right' caption='[[6fw0]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='6fw0' size='340' side='right'caption='[[6fw0]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6fw0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FW0 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6fw0]] 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=6FW0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FW0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C15:N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE'>C15</scene>, <scene name='pdbligand=E92:~{N}-(3-chlorophenyl)-4-oxidanylidene-chromene-3-carboxamide'>E92</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C15:N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE'>C15</scene>, <scene name='pdbligand=E92:~{N}-(3-chlorophenyl)-4-oxidanylidene-chromene-3-carboxamide'>E92</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fw0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fw0 OCA], [https://pdbe.org/6fw0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fw0 RCSB], [https://www.ebi.ac.uk/pdbsum/6fw0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fw0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6fw0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6fw0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Monoamine oxidase|Monoamine oxidase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Binda | [[Category: Large Structures]] | ||
[[Category: Borges | [[Category: Binda C]] | ||
[[Category: Cagide | [[Category: Borges F]] | ||
[[Category: Manzella | [[Category: Cagide F]] | ||
[[Category: Mialet-Perez | [[Category: Manzella N]] | ||
[[Category: Parini | [[Category: Mialet-Perez J]] | ||
[[Category: Reis | [[Category: Parini A]] | ||
[[Category: Uriarte | [[Category: Reis J]] | ||
[[Category: Uriarte E]] | |||
Latest revision as of 08:14, 21 November 2024
Crystal structure of human monoamine oxidase B (MAO B) in complex with chlorophenyl-chromone-carboxamideCrystal structure of human monoamine oxidase B (MAO B) in complex with chlorophenyl-chromone-carboxamide
Structural highlights
FunctionAOFB_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. Publication Abstract from PubMedMonoamine oxidase B (MAO-B) is a validated drug target for Parkinson's disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO-B in complex with three chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6-1.8 A resolution) showed that they all bind in the active site cavity of the protein with the chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with Ki values of 55, 17, and 31 nM for N-(3',4'-dimethylphenyl)-4-oxo-4 H-chromene-3-carboxamide (1), N-(3'-chlorophenyl)-4-oxo-4 H-chromene-3-carboxamide (2), and N-(3'-fluorophenyl)-4-oxo-4 H-chromene-3-carboxamide (3), respectively. These compounds were also 1000-fold more effective than l-deprenyl in reducing the cellular levels of reactive oxygen species (ROS). Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis.,Reis J, Manzella N, Cagide F, Mialet-Perez J, Uriarte E, Parini A, Borges F, Binda C J Med Chem. 2018 Apr 20. doi: 10.1021/acs.jmedchem.8b00357. PMID:29648817[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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