FRESH Lecture - Synergistic 'Substrate Activation' and 'Oxygen Activation' in Salicylate Dioxygenase from QM/MM Simulations
- Prof. dr. Johannes Kästner (University of Stuttgart)
- 12 January 2017
- Gorlaeus Building
2333 CC Leiden
- Room EM1.09
Salicylate 1,2-Dioxygenase (SDO) is the first enzyme discovered to catalyze the oxidative cleavage of a monohydroxylated aromatic compound, salicylate, in contrast to the well-known electron-rich substrates. We have investigated the mechanism of dioxygen activation in SDO by QM/MM calculations. Our study reveals that the non-heme FeII center in SDO activates salicylate and O2 synergistically by a strong covalent interaction to facilitate the reductive cleavage of O2. A covalent Salicylate-FeII-O2 complex is the reactive oxygen species in this case, where the electronic structure is best described as between the two limiting cases, FeII-O2 and FeII-O2– with partial electron transfer from the activated salicylate to O2 via the Fe center. Thus, SDO employs a synergistic strategy of ‘substrate activation’ and ‘oxygen activation’ to carry out the catalytic reaction, which is unprecedented in the family of iron dioxygenases. Moreover, O2 activation in SDO happens without the assistance of a proton source. Our study essentially opens up a new window in the mechanism of O2 activation.
S. Roy and J. Kästner Angew. Chem. Int. Ed. 55, 1168 (2016)