8JNO

Crystal structure of cytochrome P450 IkaD from Streptomyces sp. ZJ306, in complex with the substrate 10-epi-deOH-HSAF

8JNO の概要

• エントリーDOI: 10.2210/pdb8jno/pdb
• 分子名称: Cytochrome P450, PROTOPORPHYRIN IX CONTAINING FE, (1Z,3E,5S,7S,8R,9S,10S,11R,13R,15R,16S,18Z,25S)-11-ethyl-2,7-dihydroxy-10-methyl-21,26-diazapentacyclo[23.2.1.09,13.08,15.05,16]octacosa-1(2),3,18-triene-20,27,28-trione, ... (5 entities in total)
• 機能のキーワード: hydroxylation, polycyclic tetramate macrolactam, oxidoreductase, cytochrome p450
• 由来する生物種: Streptomyces sp. ZJ306
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94023.46

構造登録者

Zhang, Y.L.,Zhang, L.P.,Zhang, C.S. (登録日: 2023-06-06, 公開日: 2023-11-22, 最終更新日: 2023-12-20)

主引用文献

Jiang, P.,Jin, H.,Zhang, G.,Zhang, W.,Liu, W.,Zhu, Y.,Zhang, C.,Zhang, L.
A Mechanistic Understanding of the Distinct Regio- and Chemoselectivity of Multifunctional P450s by Structural Comparison of IkaD and CftA Complexed with Common Substrates.
Angew.Chem.Int.Ed.Engl., 62:e202310728-e202310728, 2023

PubMed Abstract: Regio- and chemoselective C-H activation at multi-positions of a single molecule is fascinating but chemically challenging. The homologous cytochrome P450 enzymes IkaD and CftA catalyze multiple C-H oxidations on the same polycyclic tetramate macrolactam (PoTeM) ikarugamycin, with distinct regio- and chemoselectivity. Herein we provide mechanistic understanding of their functional differences by solving crystal structures of IkaD and CftA in complex with ikarugamycin and unnatural substrates. Distinct conformations of the F/G region in IkaD and CftA are found to differentiate the orientation of PoTeM substrates, by causing different binding patterns with polar moieties to determine site selection, oxidation order, and chemoselectivity. Fine-tuning the polar subpocket altered the regioselectivity of IkaD, indicating that substrate re-orientation by mutating residues distal to the oxidation site could serve as an important method in future engineering of P450 enzymes.

PubMed: 37917570
DOI: 10.1002/anie.202310728

実験手法

X-RAY DIFFRACTION (2 Å)