Mechanism of Sulfide Binding by Ferric Hemeproteins

BOUBETA, FERNANDO M.; BIEZA, SILVINA A.; BRINGAS, MAURO; ESTRIN, DARÍO A.; BOECHI, LEONARDO; BARI, SARA E.

INORGANIC CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2018

0020-1669

ABSTRACT: Thereaction of hydrogen sulfide (H2S) with hemeproteins is a keyphysiological reaction; still, its mechanism and implications are not completelyunderstood. In this work we propose a combination of experimental andtheoretical tools to shed light on the reaction in the model systemmicroperoxidase 11 (MP11-FeIII) and myoglobin (Mb-FeIII),from the estimation of the intrinsic binding constants of the species H2Sand hydrosulfide (HS¯), and the computational description of the overall binding process.On one hand, our results show that H2S and HS¯ are the main reactive species inMb-FeIII, and MP11-FeIII, respectively, and that themagnitude of their intrinsic binding constants are similar to most of thebinding constants reported so far for hemeproteins systems and model compounds.On the other hand, while the binding of HS¯ to Mb-FeIIIwas negligible, the binding of H2S to MP11-FeIII was significant,providing a frame for a discriminated analysis of both species and revealingdifferential mechanistic aspects. A joint inspection of the kinetic data andthe free energy profiles of the binding processes suggests that a dissociativemechanism, with the release of a coordinated water molecule as rate limitingstep, is operative in the binding of H2S to Mb-FeIII, andthat the binding of HS¯ is prevented in the access to the protein matrix. For the MP11-FeIIIcase, where no access restrictions for the ligands are present, an associativecomponent in the mechanism seems to be operative. Overall, the results suggestthat, if accessing the active site, both H2S and HS¯are capable of binding a ferric heme moiety.