2XBK

X-ray structure of the substrate-bound cytochrome P450 PimD - a polyene macrolide antibiotic pimaricin epoxidase

2XBK の概要

• エントリーDOI: 10.2210/pdb2xbk/pdb
• 関連するPDBエントリー: 2X9P
• 分子名称: PIMD PROTEIN, PROTOPORPHYRIN IX CONTAINING FE, 4,5-DE-EPOXYPIMARICIN, ... (4 entities in total)
• 機能のキーワード: epoxidation, oxidoreductase
• 由来する生物種: STREPTOMYCES NATALENSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45794.98

構造登録者

Kells, P.M.,Ouellet, H.,Santos-Aberturas, J.,Aparicio, J.F.,Podust, L.M. (登録日: 2010-04-12, 公開日: 2010-08-04, 最終更新日: 2023-12-20)

主引用文献

Kells, P.M.,Ouellet, H.,Santos-Aberturas, J.,Aparicio, J.F.,Podust, L.M.
Structure of Cytochrome P450 Pimd Suggests Epoxidation of the Polyene Macrolide Pimaricin Occurs Via a Hydroperoxoferric Intermediate.
Chem.Biol., 17:841-, 2010

PubMed Abstract: We present the X-ray structure of PimD, both substrate-free and in complex with 4,5-desepoxypimaricin. PimD is a cytochrome P450 monooxygenase with native epoxidase activity that is critical in the biosynthesis of the polyene macrolide antibiotic pimaricin. Intervention in this secondary metabolic pathway could advance the development of drugs with improved pharmacologic properties. Epoxidation by P450 typically includes formation of a charge-transfer complex between an oxoferryl pi-cation radical species (Compound I) and the olefin pi-bond as the initial intermediate. Catalytic and structural evidence presented here suggest that epoxidation of 4,5-desepoxypimaricin proceeds via a hydroperoxoferric intermediate (Compound 0). The oxygen atom of Compound 0 distal to the heme iron may insert into the double bond of the substrate to make an epoxide ring. Stereoelectronic features of the putative transition state suggest substrate-assisted proton delivery.

PubMed: 20797613
DOI: 10.1016/J.CHEMBIOL.2010.05.026

実験手法

X-RAY DIFFRACTION (1.95 Å)