6rkb

Crystal structure of human monoamine oxidase B in complex with styrylpiperidine analogue 1

spinqualitylabelsall models 6rkb, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6rkb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: C15, FAD, K6Q Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoamine oxidase

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