Cofactor Biogenesis in Cysteamine Dioxygenase: C−F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine. (5th June 2018)

• Record Type: Journal Article
• Authors: Wang, Yifan; Griffith, Wendell P.; Li, Jiasong; Koto, Teruaki; Wherritt, Daniel J.; Fritz, Elizabeth; Liu, Aimin
• Is Part Of: Angewandte Chemie. Volume 130:Number 27(2018)
• Page Start: 8281
• Page End: 8285
• Publication Date: 2018-06-05
• Subjects: Aminosäuren -- C-H-Aktivierung -- Dioxygenasen -- Fluor -- Proteine; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201803907
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by the ambiguity as to whether or not it possesses an anticipated protein‐derived cofactor. Reported herein is the discovery and elucidation of a Cys‐Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C−S) bond. By genetically incorporating an unnatural amino acid, 3, 5‐difluoro‐tyrosine (F2 ‐Tyr), specifically into Tyr222 of human ADO, an autocatalytic oxidative carbon–fluorine bond activation and fluoride release were identified by mass spectrometry and 19 F NMR spectroscopy. These results suggest that the cofactor biogenesis is executed by a powerful oxidant during an autocatalytic process. Unlike that of cysteine dioxygenase, the crosslinking results in a minimal structural change of the protein and it is not detectable by routine low‐resolution techniques. Finally, a new sequence motif, C‐X‐Y‐Y(F), is proposed for identifying the Cys‐Tyr crosslink.