8GK3

Cytochrome P450 3A7 in complex with Dehydroepiandrosterone sulfate

8GK3 の概要

• エントリーDOI: 10.2210/pdb8gk3/pdb
• 分子名称: Cytochrome P450 3A7, PROTOPORPHYRIN IX CONTAINING FE, 17-oxoandrost-5-en-3beta-yl hydrogen sulfate, ... (4 entities in total)
• 機能のキーワード: monooxygenase, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 680805.44

構造登録者

Liu, J.,Scott, E.E. (登録日: 2023-03-16, 公開日: 2023-07-26, 最終更新日: 2023-08-30)

主引用文献

Liu, J.,Kandel, S.E.,Lampe, J.N.,Scott, E.E.
Human cytochrome P450 3A7 binding four copies of its native substrate dehydroepiandrosterone 3-sulfate.
J.Biol.Chem., 299:104993-104993, 2023

PubMed Abstract: Human fetal cytochrome P450 3A7 (CYP3A7) is involved in both xenobiotic metabolism and the estriol biosynthetic pathway. Although much is understood about cytochrome P450 3A4 and its role in adult drug metabolism, CYP3A7 is poorly characterized in terms of its interactions with both categories of substrates. Herein, a crystallizable mutated form of CYP3A7 was saturated with its primary endogenous substrate dehydroepiandrosterone 3-sulfate (DHEA-S) to yield a 2.6 Å X-ray structure revealing the unexpected capacity to simultaneously bind four copies of DHEA-S. Two DHEA-S molecules are located in the active site proper, one in a ligand access channel, and one on the hydrophobic F'-G' surface normally embedded in the membrane. While neither DHEA-S binding nor metabolism exhibit cooperative kinetics, the current structure is consistent with cooperativity common to CYP3A enzymes. Overall, this information suggests that mechanism(s) of CYP3A7 interactions with steroidal substrates are complex.

PubMed: 37392852
DOI: 10.1016/j.jbc.2023.104993

実験手法

X-RAY DIFFRACTION (2.6 Å)