View source for 9fjt


==Human Monoamine Oxidase B in complex with MC4762 inhibitor (9a) at 1.4 A resolution==
<StructureSection load='9fjt' size='340' side='right'caption='[[9fjt]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fjt]] 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=9FJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FJT 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]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IDI:~{N}-[[4-[[7-(1,3-benzoxazol-2-ylsulfanyl)-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl]phenyl]methyl]-~{N}-methyl-prop-2-yn-1-amine'>A1IDI</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=9fjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fjt OCA], [https://pdbe.org/9fjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fjt RCSB], [https://www.ebi.ac.uk/pdbsum/9fjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fjt ProSAT]</span></td></tr>
</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.
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== Publication Abstract from PubMed ==
NADPH oxidases (NOXs) are enzymes dedicated to reactive oxygen species (ROS) production and are implicated in cancer, neuroinflammation, and neurodegenerative diseases. VAS2870 is a covalent inhibitor of mainly NOX2 and NOX5. It alkylates a conserved active-site cysteine, blocking productive substrate binding. To enhance potency and selectivity toward NOXs, we conducted some chemical modifications, leading to the discovery of compound 9a that preferentially inhibits NOX2 with an IC(50) of 0.155 muM, and only upon its preactivation. We found that 9a, bearing a pargyline moiety, is also able to selectively inhibit MAOB over MAOA (465-fold) with an IC(50) of 0.182 muM, being the first-in-class dual NOX2/MAOB covalent inhibitor. Tested in the BV2 microglia neuroinflammation model, 9a decreased ROS production and downregulated proinflammatory cytokines as iNOS, IL-1beta, and IL-6 expression more efficiently than the single target inhibitors (rasagiline for MAOB and VAS2870 for NOXs) but also, more importantly, than their combination.

Design of Benzyl-triazolopyrimidine-Based NADPH Oxidase Inhibitors Leads to the Discovery of a Potent Dual Covalent NOX2/MAOB Inhibitor.,Noce B, Marchese S, Massari M, Lambona C, Reis J, Fiorentino F, Raucci A, Fioravanti R, Casteloa M, Mormino A, Garofalo S, Limatola C, Basile L, Gottinger A, Binda C, Mattevi A, Mai A, Valente S J Med Chem. 2025 Mar 5. doi: 10.1021/acs.jmedchem.4c02644. PMID:40042998<ref>PMID:40042998</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fjt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Binda C]]
[[Category: Gottinger A]]