Mechanistic insights into the crucial roles of Glu76 residue in nickel-dependent quercetin 2,4-dioxygenase for quercetin oxidative degradation

Combined QM/MM calculations and MD simulations are utilized to investigate the detailed mechanisms of reactions catalyzed by wild-type nickel-dependent quercetin 2,4-dioxygenase (Ni-QueD) and its Glu76Asp and Glu76Gln mutants. The conserved nickel-ligating Glu76 residue in the deprotonated form is found to be essential for initiating the catalytic reaction by proton coupled electron transfer process. The generated protonated Glu76 promotes the...