6YT2

Crystal Structure of human monoamine oxidase B in complex with Diphenylene iodonium (DPI)

6YT2 の概要

• エントリーDOI: 10.2210/pdb6yt2/pdb
• 分子名称: Amine oxidase [flavin-containing] B, FLAVIN-ADENINE DINUCLEOTIDE, benzo[b][1]benziodole, ... (6 entities in total)
• 機能のキーワード: monoamine oxidase, drug target, neurodegeneration, ros, flavin, mitochondrial membrane, flavoprotein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 120399.65

構造登録者

Iacovino, L.G.,Reis, J.,Mai, A.,Mattevi, A.,Binda, C. (登録日: 2020-04-23, 公開日: 2020-06-10, 最終更新日: 2024-11-13)

主引用文献

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

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: 32459875
DOI: 10.1002/cmdc.202000264

実験手法

X-RAY DIFFRACTION (1.8 Å)