Excited-state intermediates in a designer protein encoding a phototrigger caught by an X-ray free-electron laser

Xiaohong Liu, Pengcheng Liu, Hongjie Li, Zhen Xu, Lu Jia, Yan Xia, Minling Yu, Wenqin Tang, Xiaolei Zhu, Chao Chen, Yuanlin Zhang, Eriko Nango, Rie Tanaka, Fangjia Luo, Koji Kato, Yoshiki Nakajima, Shunpei Kishi, Huaxin Yu, Naoki Matsubara, Shigeki OwadaKensuke Tono, So Iwata, Long-Jiang Yu, Jian-Ren Shen, Jiangyun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

One of the primary objectives in chemistry research is to observe atomic motions during reactions in real time. Although X-ray free-electron lasers (XFELs) have facilitated the capture of reaction intermediates using time-resolved serial femtosecond crystallography (TR-SFX), only a few natural photoactive proteins have been investigated using this method, mostly due to the lack of suitable phototriggers. Here we report the genetic encoding of a xanthone amino acid (FXO), as an efficient phototrigger, into a rationally designed human liver fatty-acid binding protein mutant (termed XOM), which undergoes photo-induced C–H bond transformation with high selectivity and quantum efficiency. We solved the structures of XOM before and 10–300 ns after flash illumination, at 1.55–1.70 Å resolutions, and captured the elusive excited-state intermediates responsible for precise C–H bond activation. We expect that most redox enzymes can now be investigated by TR-SFX, using our method, to reveal reaction intermediates key for their efficiency and selectivity. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)1054-1060
Number of pages7
JournalNature Chemistry
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Fingerprint

Dive into the research topics of 'Excited-state intermediates in a designer protein encoding a phototrigger caught by an X-ray free-electron laser'. Together they form a unique fingerprint.

Cite this