6KFW

The cytochrome P450 enzyme CxnD for C-S bond formation in chuangxinmycin biosynthesis

6KFW の概要

• エントリーDOI: 10.2210/pdb6kfw/pdb
• 分子名称: CxnD, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: p450, cxnd, oxidoreductase
• 由来する生物種: Actinoplanes tsinanensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46512.51

構造登録者

Hong, B. (登録日: 2019-07-09, 公開日: 2020-07-15, 最終更新日: 2023-11-22)

主引用文献

Shi, Y.,Jiang, Z.,Hu, X.,Hu, X.,Gu, R.,Jiang, B.,Zuo, L.,Li, X.,Sun, H.,Zhang, C.,Wang, L.,Wu, L.,Hong, B.
The Cytochrome P450 Catalyzing C-S Bond Formation in S-Heterocyclization of Chuangxinmycin Biosynthesis.
Angew.Chem.Int.Ed.Engl., 60:15399-15404, 2021

PubMed Abstract: Microbial sulfur-containing secondary metabolites show various biological activities, but the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp )-H thiolation by the P450 in chuangxinmycin biosynthesis.

PubMed: 33884733
DOI: 10.1002/anie.202015814

実験手法

X-RAY DIFFRACTION (2 Å)