INVESTIGADORES
ESTRIN Dario Ariel
congresos y reuniones científicas
Título:
Access and binding of H2S to hemeproteins: the case of HbI of Lucina Pectinata
Autor/es:
D.A. ESTRIN; F. BOUBETA; L. BOECHI; S. BARI
Lugar:
Hamburgo
Reunión:
Conferencia; XIX Conference on Oxygen Binding and Sensing Proteins; 2016
Institución organizadora:
O2bip
Resumen:
Access and Binding of H2S to Hemeproteins: the Case of HbI of Lucina pectinataF. M. Boubeta1, S.E. Bari2, D.A. Estrin1, L. Boechi21Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad deBuenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires C1428EHA Argentina.2Instituto de Cálculo/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires C1428EHA Argentina.The long history of hydrogen sulfide (H2S) as a deleterious molecule was deconstructed with the discovery that sulfide species are produced and regulated in mammals and plants, with im- portant biological functions at low concentrations. At the onset of the XXI century, H2S was included in the family of gasotrasmitters (along with nitrogen oxide and carbon monoxide). In most cases, the function of H2S is related to reactions with small endogenous thiol compounds, protein thiols, metalloproteins and hemeproteins. In myoglobin and hemoglobin, diverse forms of reactivity of sulfide have been described: whereas the formation of the so-called sulfheme compounds due to the reaction of sulfide on the heme periphery has been attributed to either deleterious processes or to a detoxification shortcut, the binding of sulfide to the ferric ion of hemoglobin has been recently reported as the initial step of an oxidative, catabolic route for sulfide. The binding of sulfide to ferric heme proteins is under active debate both from the che- mical and biological standpoints. The affinity constant of Fe(III)-(sulfide) complexes described up to date ranges from ~109 M-1 (hemoglobin I of L. pectinata, HbI), to ~104 M-1 (microper- oxidase 11) at physiological pH. H2S is unique for its ability to render varying concentrations of the nucleophilic conjugate bases (HS- or S2-), either as free or bound species with expected outcomes on its further reactivity. There is no direct evidence about which species (H2S, HS- or S2-) coordinates to the iron.In this work, we performed computer simulations to shed light on the migration and binding processes of H2S species to the hemoglobin I of Lucina pectinata, which exhibits the highest affinity for the substrate measured to date. We found that H2S is the most favorable species in the migration from the bulk to the active site, through an internal pathway of the protein. After the coordination of H2S, an array of clustered water molecules modifies the active site envi- ronment, and assists in the subsequent deprotonation of the ligand, forming Fe(III)-SH-. The feasibility of the second deprotonation of the coordinated ligand is also discussed.
rds']