Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes

Abstract

Heme haloperoxidases are unique enzymes in biology that react H 2 O 2 and halides on a heme center to generate hypohalide, which reacts with a substrate by halide transfer. We studied model complexes of the active site of heme haloperoxidase and investigated the reaction mechanism starting from an iron(III)-hydrogen peroxide-heme complex. We find two stepwise proton transfers by active site Glu and His residues to form Compound I and water, whereby the second proton transfer step is rate-determining. In a subsequent reaction with chloride the oxygen atom transfer is studied to form hypohalide. Overall, the free energy of activation of the second proton transfer and oxygen atom transfer to halide are similar in energy with free energies of activation of around 20 kcal mol À 1. The calculations show that during oxygen atom transfer from Compound I to halide, significant charge-transfer happens prior to the transition state. This implies that the reaction may be enhanced in polar environments and through secondcoordination sphere effects. The studies show that the conversion of H 2 O 2 and halide on a heme center is fast and few intermediates along the reaction mechanism will have a lifetime that is long enough to enable trapping and characterization with experimental methods. A range of active site models and density functional theory methods were tested, but little effect is seen on the mechanism and optimized geometries.

Thermal contributions to the structural phase transitions of crystalline aluminum under ultrahigh pressures

“…On the one hand, it seems that the neglect of thermal contribution does not make any difference to the phase stability at room temperature because both the phase transition of FCC→HCP→BCC and the mentioned HCP stability can be successfully reproduced by the criteria of enthalpy, which indicates that, at least at room temperature, the cold energy plays a dominant role in characterizing the structural stability of crystalline Al. On the other hand, nevertheless, the exclusion of thermal effects leads to prominently different transition pressures, 171 and 378 GPa, which are consistent with the results from previous computations [33][34][35], but about 11% lower and 5% higher than those determined by DIA respectively. Although such a difference is not as large as that predicted in previous works based on phonon model [30,33], the deficiency of the criterion of enthalpy at 0K is apparently manifested by much more deviations of the transition pressures from all the exiting experimental data as listed in Table .I.…”

“…The discrepancy between theoretical predictions and experimental measurements also exists in the pressureinduced structural phase transitions of the crystalline aluminum (Al), which serves as a benchmark system for high-pressure studies due to its simple sp electron shells [25,26]. In spite of the early experiments [27,28] and ab initio phonon computations [29] reporting the FCC structure to be stable up to 1000 GPa at room temperature, more theoretical works predicted a FCC→HCP→BCC phase transition within 600 GPa [30][31][32][33][34][35], which was observed by following experiments at around 220 (320) GPa [36][37][38] or 198 (360) GPa [39]for the FCC→HCP (HCP→BCC) respectively. Compared with the experimental measurements of the two transition pressures, the most accurately predicted ones so far were obtained on the basis of ab initio computations combined with semi-empirical SESAME equations of state (EOS) [35], at 185 and 389 GPa for the two transformations respectively, which improve the theoretical accuracy but still deviate about 15% from the results in Ref.…”

Bioengineering of Cytochrome P450 OleTJE: How Does Substrate Positioning Affect the Product Distributions?

“…The Fe-O distances are in a narrow range from 1.626 to 1.634Å. These distances match the previously calculated CpdI structures of heme enzymes representing the P450s [2,25,[32][33][34][35][36][37][38][39][40][41][42] and peroxidases [72][73][74] well. As seen before, the doublet and quartet spin states are calculated to be within 1 kcal mol -1 for each of the snapshots.…”

Computational Study of the Peroxygenase Mechanism Catalyzed by Hemoglobin Dehaloperoxidase Involved in the Degradation of Chlorophenols

“…The QM/MM method has been established to be a reliable tool for exploring the enzymatic reactions, − also including some heme enzymes. − In past decades, the QM/MM approach and improved QM method have been widely employed in the studies of biodegradation of pollutants. − Herein, we performed QM/MM calculations to investigate the peroxygenase mechanism of the oxidation of 4-Cl- o -cresol catalyzed by DHP B.…”