Interaction of metmyoglobin with sulfur species: migration and acidity of HSSH/HSS-

CÓRDOVA, JONATHAN ALEXIS; PALERMO, JUAN CRUZ; SEMELAK, JONATHAN ALEXIS; ESTRIN, DARÍO ARIEL; BARI, SARA ELIZABETH; CAPECE, LUCIANA

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Biofisica; 2022

Sociedad Argentina de Biofisica

The role of inorganic sulfur species in biological systems has gained considerable interest since the recognition of sulfanes, particularly dihydrogen sulfide or sulfane, H2S, disulfane, HSSH, trisulfane, HSSSH, and their conjugate bases, as endogenous species and mediators of signaling functions in different tissues. In this work, we focused on the migration of the ligand from the bulk to the active site of metmyoglobin. In this context, we studied the migration of disulfane (HSSH) and its conjugated base (HSS-) from the bulk to the heme myoglobin active site. As reported experimental data is not conclusive, it was important to determine which species are present in the bio-relevant environment. Thus, the acidity constant (pKa) of HSSH was also computed, in order to estimate the population of each form at a certain pH. Additionally, to have a complete perspective about the speciation of bio-relevant inorganic sulfur species, we estimated the pKas of HSSSH and of the radical sulfanyl (HS·), recognized as products or intermediates in certain biological processes.For these purposes, QM calculations were used to estimate the pKa of the selected inorganic sulfur species, following two independent approaches developed by members of the group, and we applied a combination of computer simulation techniques, including steered classical molecular dynamics simulations and Jarzynski’s inequality to determine the free energy profile of migration of the ligand to the active site.Our results suggest that HSSH and HSSSH are more acidic than H2S, while the pKa of the HS· radical is similar to that of H 2S. Migration free energy profiles of HSSH/HSS- in metmyoglobin exhibit a similar behavior to the previously observed for the H2S/HS-, and the neutral HSSH migrates preferentially to the active site of metmyoglobin, in the same way as H2S does. Altogether the results describe the complete picture of HSSH/HSS- metmyoglobin, and provide an insight into the speciation of HSSSH/HSSS- and HS*/S*- under bio-relevant environments-