6YT2
Crystal Structure of human monoamine oxidase B in complex with Diphenylene iodonium (DPI)
Summary for 6YT2
| Entry DOI | 10.2210/pdb6yt2/pdb |
| Descriptor | Amine oxidase [flavin-containing] B, FLAVIN-ADENINE DINUCLEOTIDE, benzo[b][1]benziodole, ... (6 entities in total) |
| Functional Keywords | monoamine oxidase, drug target, neurodegeneration, ros, flavin, mitochondrial membrane, flavoprotein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 120399.65 |
| Authors | Iacovino, L.G.,Reis, J.,Mai, A.,Mattevi, A.,Binda, C. (deposition date: 2020-04-23, release date: 2020-06-10, Last modification date: 2024-11-13) |
| Primary citation | Iacovino, L.G.,Reis, J.,Mai, A.,Binda, C.,Mattevi, A. Diphenylene Iodonium Is a Noncovalent MAO Inhibitor: A Biochemical and Structural Analysis. Chemmedchem, 15:1394-1397, 2020 Cited by PubMed Abstract: Diphenylene 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 and reversible MAO inhibitor with K values of 1.7 and 0.3 μM 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 that the inhibition mechanism does not involve a reaction with the reduced flavin. This binding and inhibitory activity against the MAOs, two major reactive oxygen species (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. PubMed: 32459875DOI: 10.1002/cmdc.202000264 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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