6BPT

Crystal structure of ferrous form of the uncrosslinked F2-Tyr157 human cysteine dioxygenase

6BPT の概要

• エントリーDOI: 10.2210/pdb6bpt/pdb
• 分子名称: Cysteine dioxygenase type 1, FE (II) ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: cysteine, cys-tyr cofactor, iron, unnatural amino acid, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23698.12

構造登録者

Liu, A.,Li, J.,Shin, I. (登録日: 2017-11-26, 公開日: 2018-07-04, 最終更新日: 2023-11-15)

主引用文献

Li, J.,Griffith, W.P.,Davis, I.,Shin, I.,Wang, J.,Li, F.,Wang, Y.,Wherritt, D.J.,Liu, A.
Cleavage of a carbon-fluorine bond by an engineered cysteine dioxygenase.
Nat. Chem. Biol., 14:853-860, 2018

PubMed Abstract: Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a genetic method. The catalytically active variants were obtained with a thioether bond between Cys93 and the halogen-substituted Tyr157, and we determined the crystal structures of both wild-type and engineered CDO variants in the purely uncross-linked form and with a mature cofactor. Along with mass spectrometry and F NMR, these data indicated that the enzyme could catalyze oxidative C-F or C-Cl bond cleavage, resulting in a substantial conformational change of both Cys93 and Tyr157 during cofactor assembly. These findings provide insights into the mechanism of Cys-Tyr cofactor biogenesis and may aid the development of bioinspired aromatic carbon-halogen bond activation.

PubMed: 29942080
DOI: 10.1038/s41589-018-0085-5

実験手法

X-RAY DIFFRACTION (2.402 Å)