Heme iron as target for inorganic sulfide

BARI, SARA ELIZABETH; BIEZA, SILVINA ANDREA; BRINGAS, MAURO; PALERMO, JUAN CRUZ; BOECHI, LEONARDO; ESTRIN, DARÍO ARIEL

Barcelona

Congreso; XXth International Conference on Oxygen Binding and Sensing Proteins; 2018

Molecules

Hydrogen sulfide, H2S, has been recognized as an endogenous signaling molecule, capable of interacting with thiols, other small gaseous signaling molecules, and certain metal containing biomolecules. We focused on the metal centered reactions ofinorganic sulfide (H2S/HS-/S2-) with FeIII hemes, representatively evoked by the high affinity coordination to the hemoglobin I of the clam Lucina pectinata.However, the outcome of the interaction of sulfide with FeIII hemes is diverse, and coordination, reduction, or inertness have been reported. Concerning the coordination, using the model microperoxidase 11, FeIIIMP11, a hemepeptide with a histidine as proximal ligand and no distal contributions, we reported on the formation of a moderately stable FeIII-sulfide complex at pH 6.8. The Kaff = 4.6 x 103 M-1 is in the lower limit of those measured for sulfide binding FeIII hemeproteins, and represents an estimate for the contribution of the proximal ligand to the coordination reaction.An inspection of the dependence of the binding constant as a function of pH revealed that both the conjugate anion hydrosulfide, SH- , and H2S are capable of binding the FeIII heme (kon ≈ 104 and 103 M-1s-1, respectively). Instead, onlyH2S behaved as binding species and the anion was inert when the target was metmyoglobin. With the aid of computational tools, these results have been interpreted in terms of the role of the protein scaffold in the selection of the active species: while the freely accessible heme iron of FeIIIMP11 can be reached either by HSor H2S, the anion is prevented to access the heme active site of metmyoglobin.After coordination, diverse ferric heme compounds have been shown to yield the corresponding ferrous derivative with different timescales; e.g.: the reduction has been suggested to be mediating a proposed mechanism of detoxification of sulfide by human hemoglobin.A preliminary analysis of the reduction mechanism will be presented, along with the potential impact of the reduction on the formation of physiologically relevant polysulfide species.