Heme Iron as Target for Inorganic Sulfide

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

Barcelona

Conferencia; XXth International Conference on Oxygen Sensing and Binding Proteins (O2BiP); 2018

Heme Iron as Target for Inorganic SulfideFernando M. Boubeta,a Silvina A. Bieza,a Juan Cruz Palermo,a Mauro Bringas,a,b Leonardo Boechi,c Darío A. Estrin,a,b Sara E. Bariaa Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química de los Materiales, Medio Ambiente y Energía. Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina.b Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física. Buenos Aires, Argentina.c Universidad de Buenos Aires. Instituto de Cálculo. Facultad de Ciencias Exactas y Naturales. Buenos Aires, Argentina.bari@qi.fcen.uba.arHydrogen 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 of inorganic sulfide (H2S/HS-/S2-) with FeIII hemes, representatively evoked by the high affinity coordination (Kaff= 109 M-1) to the hemoglobin I of the clam Lucina pectinata.1 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.2 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, only H2S 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 HS- or 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;3 e.g.: the reduction has been suggested to be mediating a proposed mechanism of detoxification of sulfide by human hemoglobin.4 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.References1. Kraus, D.W.; Wittenberg, J.B., J. Biol. Chem., 1990, 265, 16043-53.2. Bieza, S.A. et al., Inorg. Chem, 2015, 54, 527-33 (10.1021/ic502294z).3. Mittra, K. et al., Inorg. Chem, 2017, 56, 39-25 (10.1021/acs.inorgchem.6b02878).4. Vitvitsky, V. et al., J. Biol. Chem, 2015, 290, 8310-20 (10.1074/jbc.M115.639831).