View source for 6rkp


==Crystal structure of human monoamine oxidase B in complex with styrylpiperidine analogue 84==
<StructureSection load='6rkp' size='340' side='right'caption='[[6rkp]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rkp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RKP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RKP 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=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K72:1-[(~{E})-prop-1-enyl]-4-[(~{E})-2-[4-(trifluoromethyl)phenyl]ethenyl]piperidine'>K72</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Monoamine_oxidase Monoamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rkp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rkp OCA], [http://pdbe.org/6rkp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rkp RCSB], [http://www.ebi.ac.uk/pdbsum/6rkp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rkp ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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 ==
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 6rkp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Monoamine oxidase]]
[[Category: Binda, C]]
[[Category: Colettis, N]]
[[Category: Dolsak, A]]
[[Category: Gobec, S]]
[[Category: Higgs, J]]
[[Category: Iacovino, L G]]
[[Category: Kamecki, F]]
[[Category: Knez, D]]
[[Category: Kos, J]]
[[Category: Mangialavori, I]]
[[Category: Marder, N M]]
[[Category: Pislar, A]]
[[Category: Sova, M]]
[[Category: Trontelj, J]]
[[Category: Zakelj, S]]
[[Category: Drug target]]
[[Category: Flavin]]
[[Category: Flavoprotein]]
[[Category: Isomer]]
[[Category: Mitochondrial membrane]]
[[Category: Neurodegeneration]]