View source for 6rkb


==Crystal structure of human monoamine oxidase B in complex with styrylpiperidine analogue 1==
<StructureSection load='6rkb' size='340' side='right'caption='[[6rkb]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rkb]] 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=6RKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RKB 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]] 2.3&#8491;</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=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=K6Q:4-[(~{E})-2-(4-fluorophenyl)ethenyl]-1-[(~{E})-prop-1-enyl]piperidine'>K6Q</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=6rkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rkb OCA], [https://pdbe.org/6rkb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rkb RCSB], [https://www.ebi.ac.uk/pdbsum/6rkb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rkb 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 ==
The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis- and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.

Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B.,Knez D, Colettis N, Iacovino LG, Sova M, Pislar A, Konc J, Lesnik S, Higgs J, Kamecki F, Mangialavori I, Dolsak A, Zakelj S, Trontelj J, Kos J, Binda C, Marder M, Gobec S J Med Chem. 2020 Jan 22. doi: 10.1021/acs.jmedchem.9b01886. PMID:31917923<ref>PMID:31917923</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rkb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoamine oxidase|Monoamine oxidase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Binda C]]
[[Category: Colettis N]]
[[Category: Dolsak A]]
[[Category: Gobec S]]
[[Category: Higgs J]]
[[Category: Iacovino LG]]
[[Category: Kamecki F]]
[[Category: Knez D]]
[[Category: Kos J]]
[[Category: Mangialavori I]]
[[Category: Marder NM]]
[[Category: Pislar A]]
[[Category: Sova M]]
[[Category: Trontelj J]]
[[Category: Zakelj S]]