6OO9

Human CYP3A4 bound to a drug mibefradil

6OO9 の概要

• エントリーDOI: 10.2210/pdb6oo9/pdb
• 分子名称: Cytochrome P450 3A4, PROTOPORPHYRIN IX CONTAINING FE, (1S,2S)-2-(2-{[3-(1H-benzimidazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, ... (6 entities in total)
• 機能のキーワード: substrate, complex, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57072.20

構造登録者

Sevrioukova, I.F. (登録日: 2019-04-22, 公開日: 2019-09-11, 最終更新日: 2023-10-11)

主引用文献

Sevrioukova, I.F.
Structural Insights into the Interaction of Cytochrome P450 3A4 with Suicide Substrates: Mibefradil, Azamulin and 6',7'-Dihydroxybergamottin.
Int J Mol Sci, 20:-, 2019

PubMed Abstract: Human cytochrome P450 3A4 (CYP3A4) is the most important drug-metabolizing enzyme. Some drugs and natural compounds can act as suicide (mechanism-based) inactivators of CYP3A4, leading to unanticipated drug-drug interactions, toxicity and therapeutic failures. Despite significant clinical and toxicological implications, the mechanism-based inactivation remains incompletely understood. This study provides the first direct insights into the interaction of CYP3A4 with three suicide substrates: mibefradil, an antihypertensive drug quickly withdrawn from the market; a semi-synthetic antibiotic azamulin; and a natural furanocoumarin, 6',7'-dihydroxybergamottin. Novel structural findings help better understand the suicide substrate binding and inhibitory mechanism, and can be used to improve the predictability of the binding ability, metabolic sites and inhibitory/inactivation potential of newly developed drugs and other chemicals relevant to public health.

PubMed: 31480231
DOI: 10.3390/ijms20174245

実験手法

X-RAY DIFFRACTION (2.25 Å)