6BPU

Crystal structure of ferrous form of the F2-Tyr157 human cysteine dioxygenase with both uncrosslinked and crosslinked cofactor

Summary for 6BPU

• Entry DOI: 10.2210/pdb6bpu/pdb
• Descriptor: Cysteine dioxygenase type 1, FE (II) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: cysteine, cys-tyr cofactor, iron, unnatural amino acid, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 23694.15

Authors

Liu, A.,Li, J.,Shin, I. (deposition date: 2017-11-26, release date: 2018-07-04, Last modification date: 2023-11-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)