The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological Conditions.
The phenolic hydroxyl group of tyrosine residue plays a crucial role in the structure and function of many proteins. However, little study has been reported about its modification by chemical agents under physiological conditions. In this study, we found, unexpectedly, that the phenolic hydroxyl group of tyrosine can be rapidly and efficiently modified by tetrafluoro-1,4-benzoquinone and other polyhalogenated quinones, which are the major genotoxic and carcinogenic quinoid metabolites of polyhalogenated aromatic compounds. The modification was found to be mainly due to the formation of a variety of fluoroquinone-O-tyrosine conjugates and their hydroxylated derivatives via nucleophilic substitution pathway. Analogous modifications were observed for tyrosine-containing peptides. Further studies showed that the blockade of the reactive phenolic hydroxyl group of tyrosine in the substrate peptide, even by very low concentration of tetrafluoro-1,4-benzoquinone, can prevent the kinase catalyzed tyrosine phosphorylation. This is the first report showing the exceptionally facile chemical modification of the phenolic hydroxyl group of tyrosine by polyhalogenated quinones under normal physiological conditions, which may have potential biological and toxicological implications.
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences, the Chinese Academy of Sciences , 18 Shuangqin Road, Haidian District, Beijing 100085, P. R. China.
Na
N
Qu
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences, the Chinese Academy of Sciences , 18 Shuangqin Road, Haidian District, Beijing 100085, P. R. China.
Feng
F
Li
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences, the Chinese Academy of Sciences , 18 Shuangqin Road, Haidian District, Beijing 100085, P. R. China.
Bo
B
Shao
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences, the Chinese Academy of Sciences , 18 Shuangqin Road, Haidian District, Beijing 100085, P. R. China.
Jie
J
Shao
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, P. R. China.|Tianjin Research Centre of Basic Medical Sciences, Tianjin Medical University , Tianjin 300070, P. R. China.
Guijin
G
Zhai
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, P. R. China.
Fuyi
F
Wang
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences and University of the Chinese Academy of Sciences, the Chinese Academy of Sciences , 18 Shuangqin Road, Haidian District, Beijing 100085, P. R. China.
Ben-Zhan
BZ
Zhu
D006878:Hydroxides / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D010636:Phenols / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry*
D006878:Hydroxides; D010455:Peptides; D010636:Phenols; D011809:Quinones; D014443:Tyrosine; C031356:hydroxide ion