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 vol. 57 p. 7591 - 7600

0020-1669

: The reaction of hydrogen sulfide (H2S) withhemeproteins is a key physiological reaction; still, itsmechanism and implications are not completely understood.In this work, we propose a combination of experimental andtheoretical tools to shed light on the reaction in model systemmicroperoxidase 11 (MP11-FeIII) and myoglobin (Mb-FeIII),from the estimation of the intrinsic binding constants of thespecies H2S and hydrosulfide (HS−), and the computationaldescription of the overall binding process. Our results showthat H2S and HS− are the main reactive species in Mb-FeIII andMP11-FeIII, respectively, and that the magnitude of theirintrinsic binding constants are similar to most of the bindingconstants reported so far for hemeproteins systems and modelcompounds. However, while the binding of HS− to Mb-FeIII was negligible, the binding of H2S to MP11-FeIII was significant,providing a frame for a discriminated analysis of both species and revealing differential mechanistic aspects. A joint inspection ofthe kinetic data and the free energy profiles of the binding processes suggests that a dissociative mechanism with the release of acoordinated water molecule as rate limiting step is operative in the binding of H2S to Mb-FeIII and that the binding of HS− isprevented in the access to the protein matrix. For the MP11-FeIII case, where no access restrictions for the ligands are present,an associative component in the mechanism seems to be operative. Overall, the results suggest that if accessing the active sitethen both H2S and HS− are capable of binding a ferric heme moiety.