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 PubMedDiphenylene iodonium (DPI) is known for its inhibitory activities against many flavin- and heme-dependent enzymes and is often used as an NADPH oxidase inhibitor. We probed the efficacy of DPI on two well-known drug targets, the human monoamine oxidases MAO A and B. UV-visible spectrophotometry and steady-state kinetics experiments demonstrate that DPI acts as a competitive MAO inhibitor with Ki values of 1.7 microM and 0.3 microM for MAO A and MAO B, respectively. Elucidation of the crystal structure of human MAO B bound to the inhibitor revealed that DPI binds deeply in the active-site cavity to establish multiple hydrophobic interactions with the surrounding side chains and the flavin. These data prove that DPI is a genuine MAO inhibitor and the inhibition mechanism does not involve a reaction with the reduced flavin. This binding and inhibitory activity against MAOs, two major ROS-producing enzymes, will have to be carefully considered when interpreting experiments that rely on DPI for target validation and chemical biology studies on ROS functions. Diphenylene iodonium is a non-covalent MAO inhibitor: a biochemical and structural analysis.,Iacovino LG, Reis J, Mai A, Binda C, Mattevi A ChemMedChem. 2020 May 27. doi: 10.1002/cmdc.202000264. PMID:32459875[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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