3P3X

Crystal Structure of the Cytochrome P450 Monooxygenase AurH (nterm-AurH-I) from Streptomyces Thioluteus

3P3X の概要

• エントリーDOI: 10.2210/pdb3p3x/pdb
• 関連するPDBエントリー: 3P3L 3P3O 3P3Z
• 分子名称: Cytochrome P450, PROTOPORPHYRIN IX CONTAINING FE, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: cytochrome p450 monooxygenase, oxidation of deoxyaureothin to aureothin, oxidoreductase
• 由来する生物種: Streptomyces Thioluteus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94006.52

構造登録者

Zocher, G.,Richter, M.E.A.,Mueller, U.,Hertweck, C. (登録日: 2010-10-05, 公開日: 2011-02-16, 最終更新日: 2024-02-21)

主引用文献

Zocher, G.,Richter, M.E.,Mueller, U.,Hertweck, C.
Structural fine-tuning of a multifunctional cytochrome p450 monooxygenase.
J.Am.Chem.Soc., 133:2292-2302, 2011

PubMed Abstract: AurH is a unique cytochrome P450 monooxygenase catalyzing the stepwise formation of a homochiral oxygen heterocycle, a key structural and pharmacophoric component of the antibiotic aureothin. The exceptional enzymatic reaction involves a tandem oxygenation process including a regio- and stereospecific hydroxylation, followed by heterocyclization. For the structural and biochemical basis of this unparalleled sequence, four crystal structures of AurH variants in different conformational states and in complex with the P450 inhibitor ancymidol were solved, which represent the first structures of the CYP151A group. Structural data in conjunction with computational docking, site-directed mutagenesis, and chemical analyses unveiled a switch function when recognizing the two substrates, deoxyaureothin and the hydroxylated intermediate, thus allowing the second oxygenation-heterocyclization step. Furthermore, we were able to modify the chemo- and regioselectivity of AurH, yielding mutants that catalyze the regioselective six-electron transfer of a nonactivated methyl group to a carboxylic acid via hydroxyl and aldehyde intermediates.

PubMed: 21280577
DOI: 10.1021/ja110146z

実験手法

X-RAY DIFFRACTION (2.3 Å)