7B0V

Crystal Structure of human monoamine oxidase B in complex with (E)-3-phenyl-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one

7B0V の概要

• エントリーDOI: 10.2210/pdb7b0v/pdb
• 分子名称: Amine oxidase [flavin-containing] B, FLAVIN-ADENINE DINUCLEOTIDE, (E)-3-phenyl-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one, ... (6 entities in total)
• 機能のキーワード: monoamine oxidase, drug target, neurodegeneration, flavin, chalcone, 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: 120656.36

構造登録者

Iacovino, L.G.,Binda, C. (登録日: 2020-11-23, 公開日: 2021-11-03, 最終更新日: 2024-11-06)

主引用文献

Iacovino, L.G.,Pinzi, L.,Facchetti, G.,Bortolini, B.,Christodoulou, M.S.,Binda, C.,Rastelli, G.,Rimoldi, I.,Passarella, D.,Di Paolo, M.L.,Dalla Via, L.
Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase-B.
Acs Med.Chem.Lett., 12:1151-1158, 2021

PubMed Abstract: A library of monosubstituted chalcones (-) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (, , and ) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with and showing the best profiles. In particular, exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases.

PubMed: 34262643
DOI: 10.1021/acsmedchemlett.1c00238

実験手法

X-RAY DIFFRACTION (2.3 Å)