Mechanistic Insights into Ring Cleavage of Hydroquinone by PnpCD from Quantum Mechanical/Molecular Mechanical Calculations
PnpCD is a mononuclear non-heme iron(II) dioxygenases containing an unusual 2His-1Glu-1Asn metal binding motif. To get insights into the catalytic mechanism of ring opening of hydroquinone by PnpCD, the hybrid quantum mechanics/molecular mechanics calculations have been performed by using two models with different protonation state of substrate (nonionized and ionized forms of the Fe-bound hydroxyl group of hydroquinone). In both cases, the structure of the reactive Fe-O2 species reveals a trigonal bipyramidal complex, in which Asn258 is no longer coordinated to the iron center. The catalytic process mainly involves the attack of superoxo radical, O-O bond cleavage, three-membered ring closure and opening, attack of the Fe-bound oxyl radical, and ring-opening of seven-membered ring. The transition state for the peroxo O-O bond cleavage was found to be rate-determining transition state. The second-sphere Glu248 serves as a proton acceptor to deprotonate the unbound substrate hydroxyl group, and hence facilitating the electron transfer between substrate and dioxygen. The first-sphere Glu262 can act as an acid-base catalyst to lower the rate-limiting barrier, thus providing a useful clue for improving the catalytic efficiency.
- This article is part of the themed collection: Mechanistic, computational & physical organic chemistry in OBC