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

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

Congreso; L Reunión de la Sociedad Argentina de Biofísica; 2022

The role of inorganic sulfur species in biological systems has gained considerable interestsince the recognition of sulfanes, particularly dihydrogen sulfide or sulfane, H2S,disulfane, HSSH, trisulfane, HSSSH, and their conjugate bases, as endogenous speciesand 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 ofmetmyoglobin. In this context, we studied the migration of disulfane (HSSH) and itsconjugated base (HSS-) from the bulk to the heme myoglobin active site. As reportedexperimental data is not conclusive, it was important to determine which species arepresent in the bio-relevant environment. Thus, the acidity constant (pKa) of HSSH wasalso 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-relevantinorganic 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 selectedinorganic sulfur species, following two independent approaches developed by membersof the group, and we applied a combination of computer simulation techniques, includingsteered classical molecular dynamics simulations and Jarzynski’s inequality to determinethe 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 theHS· radical is similar to that of H 2S. Migration free energy profiles of HSSH/HSS- inmetmyoglobin exhibit a similar behavior to the previously observed for the H2S/HS-, andthe neutral HSSH migrates preferentially to the active site of metmyoglobin, in the sameway as H2S does. Altogether the results describe the complete picture of HSSH/HSSmetmyoglobin,and provide an insight into the speciation of HSSSH/HSSS- and HS./S.-under bio-relevant environments.Keywords: reactive sulfur species (RSS), metmyoglobin, computational chemistryAcknowldegmentsAgencia I+D+i and DQIAQF/INQUIMAE