Cysteine dioxygenase catalyzed C-F bond cleavage: An in silico approach

Cysteine dioxygenase (CDO) is a vital enzyme that can regulate balance of cysteine in living organism and play a decisive role in human sulfur metabolism. However, the detailed catalytic process is still obscure. Here the catalytic mechanism of CDO toward 3,5-difluoro-1-tyrosine was investigated by combining quantum mechanics/ molecular mechanics (QM/MM) method. The results show that C-F bond cleavage is the rate-determining step with an energy barrier of 18.8 kcal/mol. Furthermore, the electrostatic influence of active site residues was studied and residues Asp87, Phe161 were highlighted as potential targets for future mutations.