Binding mechanism of disulfide species to ferric hemeproteins: The case of metmyoglobin

CÓRDOVA, JONATHAN ALEXIS; PALERMO, JUAN CRUZ; ESTRIN, DARÍO A.; BARI, SARA E.; CAPECE, LUCIANA

JOURNAL OF INORGANIC BIOCHEMISTRY

ELSEVIER SCIENCE INC

Año: 2023 vol. 247

0162-0134

The interactions of the heme iron of hemeproteins with sulfide and disulfide compounds are of potential interestas physiological signaling processes. While the interaction with hydrogen sulfide has been described computa­tionally and experimentally, the reaction with disulfide, and specifically the molecular mechanism for ligandbinding has not been studied in detail. In this work, we study the association process for disulfane and itsconjugate base disulfanide at different pH conditions. Additionally, by means of advanced sampling techniquesbased on multiple steered molecular dynamics, we provide free energy profiles for ligand migration for bothacid/base species, showing a similar behavior to the previously reported for the related H 2 S/HS‾ pair. Finally, westudied the ligand interchange reaction (H 2 O/H 2 S, HS‾ and H 2 O/HSSH, HSS‾) by means of hybrid quantummechanics-molecular mechanics calculations. We show that the anionic species are able to displace more effi­ciently the H 2 O bound to the iron, and that the H-bond network in the distal cavity can help the neutral species toperform the reaction. Altogether, we provide a molecular explanation for the experimental information and showthat the global association process depends on a fine balance between the migration towards the active site andthe ligand interchange reaction.