title: Access and Binding of H2S to Hemeproteins: The Case of HbI of Lucina pectinata.
abstract: Hydrogen sulfide (H2S) was recently discovered as a gasotransmitter, capable of coordinating to the heme iron of hemeproteins. H2S is unique for its ability to render varying concentrations of the nucleophilic conjugate bases (HS(-) or S(2-)), either as free or bound species with expected outcomes on its further reactivity. There is no direct evidence about which species (H2S, HS(-), or S(2-)) coordinates to the iron. We performed computer simulations to address 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 environment, 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.
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires C1428EHA, Argentina.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Boubeta
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires C1428EHA, Argentina.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Bari
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires C1428EHA, Argentina.
authors.forename: Dario A
authors.initials: DA
authors.lastname: Estrin
authors.affiliation: Instituto de Cálculo/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires C1428EHA, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Boechi
mesh_terms: D000818:Animals; D001665:Binding Sites; D049872:Bivalvia / Q000737:chemistry*; D006420:Hemeproteins / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry*; D006862:Hydrogen Sulfide / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
chemical_list: D006420:Hemeproteins; D006454:Hemoglobins; D006862:Hydrogen Sulfide