Citation

Surducan M, Brânzanic AMV, Silaghi-Dumitrescu R. International Journal of Quantum Chemistry 2018; 118(19).

Copyright

(Copyright © 2018)

DOI

10.1002/qua.25697

PMID

unavailable

Abstract

Sulfite reductase (SiR) catalyzes a six electron and six proton reduction of sulfite to sulfide. Similarly to the cytochrome P450 (cytP450) family, the active site in SiR contains a (partially reduced) heme bound axially to a cysteinate ligand--though with an extra Fe4S4 cluster. Fe(III)SO2−, Fe(III)SOH−, and Fe(III)SO(H2) intermediates have been proposed for the catalytic cycle of SiR, leading to a formally Fe(V)S species--akin to the widely accepted reaction mechanism in cytP450. Here, density functional theory (DFT) data is reported for of such FeSO(H2) intermediates. The Fe(III)SO2− models display relatively high energies for homolytic bond breaking compared to their isomeric oxygen-bound Fe(III)OS2− models, and thus offer a better alternative in terms of avoiding radical side products able to induce enzyme suicide. This could be due to the fact that the (iron-bound) sulfur is more active from a redox standpoint compared to oxygen, thus permitting the departing oxygen to maintain a redox-inert state. Di-protonation of the oxygen is computed to lead to a compound I type Fe(IV)S coupled to a porphyrin radical anion--consistent with an intermediate previously observed by x-ray crystallography. © 2018 Wiley Periodicals, Inc.

Language: en

Keywords

Oxygen; Iron compounds; Reduction; X ray crystallography; Peroxides; peroxide; Porphyrins; Sulfur compounds; Catalytic cycles; cytP450; Density functional theory; heme; Homolytic bonds; Lead compounds; Proton reduction; Reaction intermediates; Reaction mechanism; sulfite reductase; Sulfite reductase; sulfur oxide; Sulfur oxide