6OOB

Human CYP3A4 bound to a suicide substrate

6OOB の概要

• エントリーDOI: 10.2210/pdb6oob/pdb
• 分子名称: Cytochrome P450 3A4, PROTOPORPHYRIN IX CONTAINING FE, 4-{[(2Z,6S)-6,7-dihydroxy-3,7-dimethyloct-2-en-1-yl]oxy}-7H-furo[3,2-g][1]benzopyran-7-one, ... (4 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: 56746.71

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insights into the interaction of CYP3A4 with three suicide substrates: mibefradil, an antihypertensive drug quickly withdrawn from the market; a semi-synthetic antibiotic azamulin; and a natural furanocoumarin, 6',7'-dihydroxybergamottin.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 (2.202 Å)