Tyr 118-Mediated Electron Transfer is Key to the Chlorite Decomposition in Heme-Dependent Chlorite Dismutase

Abstract

Chlorite dismutase (Cld) is a crucial enzyme that catalyzes the decomposition of chlorite ions into chloride ions (Cl − ) and molecular oxygen (O 2 ). Despite playing an important role in the detoxification of toxic chlorite ions, the mechanism of cleavage of the Cl−O bond by Cld remains highly debatable. The present study highlights the mechanism of such Cl−O bond cleavage in Cld using sophisticated computational tools such as hybrid quantum mechanical/molecular mechanical calculations and long-time scale molecular dynamics simulations. Here, we show that Cld forms a high spin ferric hexacoordinated substrate adduct in the presence of a chlorite ion, which subsequently reduces to a ferrous state. Our study shows a stepwise pathway with the homolytic cleavage of the Cl−O bond that produces a high spin Fe(III)−OH species and a diradicaloid species formed by the combination of a chlorine-based ClO • radical and a protein-based tyrosine118 • radical. The findings provide significant insights into Cl−O bond cleavage and O 2 formation which shows a crucial role of the tyrosine118 during the electron transfer process.

Directed Evolution of Protoglobin Optimizes the Enzyme Electric Field

“…The substrate benzyl acrylate was docked into the active site using AutoDock Vina. , The setup for the MD simulation was done via Amber 22 and AmberTools 22 modules. , The active site parameters for the carbene–substrate intermediates encompassing the heme, Fe, carbene, and an axial histidine were derived using AmberTool’s Metal Center Parameter Builder (MCPB) v3.0 . This protocol has been successfully utilized to model several metal containing systems especially hemes and nonheme iron complexes. − The GAFF tool in Antechamber generated the topology for the substrate benzyl acrylate. The protonation states of the protein in the carbene–substrate intermediate were determined using Chimera routines, and the parameters for the rest of the protein were generated using the AmberFF19SB force field.…”