The mechanism of the H2O2 disproportionation catalyzed by the manganese catalase (MnCat) KatB was studied using the hybrid density functional theory B3LYP and the quantum chemical cluster approach. Compared to the previous mechanistic study at the molecular level for the Thermus thermophilus MnCat (TTC), more modern methodology was used and larger models of increasing sizes were employed with the help of the high-resolution X-ray structure. In the reaction pathway suggested for KatB using the Large chemical model, the O-O homolysis of the first substrate H2O2 occurs through a μ-η1:η1 coordination mode and requires a barrier of 10.9 kcal/mol. In the intermediate state of the bond cleavage, two hydroxides form as terminal ligands of the dimanganese cluster at the Mn2(III,III) oxidation state. One of the two Mn(III)-OH- moieties and a second-sphere tyrosine stabilize the second substrate H2O2 in the second-sphere of the active site via hydrogen bonding interactions. The H2O2, unbound to the metals, is first oxidized into HO2· through a proton-coupled electron transfer (PCET) step with a barrier of 9.5 kcal/mol. After the system switches to the triplet surface, the uncoordinated HO2· replaces the product water terminally bound to the Mn(II) and is then oxidized into O2 spontaneously. Transition states with structural similarities to those obtained for TTC, where μ-η2-OH-/O2- groups play important roles, were found to be higher in energy.
Keywords: Computational chemistry; Density functional theory; Manganese catalase.