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

Mechanism of Peroxynitrite Interaction with Ferric M. tuberculosis Nitrobindin: A Computational Study

“… This result clearly suggests that for the neutral species (ONOOH), the binding is facilitated compared to that for the anionic species (ONOO – ). This behavior has been previously described in other heme proteins for this ligand and for other ligands, such as hydrogen sulfide or disulfane . Generally, the higher k on observed for the neutral species has been attributed to the facilitated migration from the solvent to the distal cavity. − However, in Mt -Nb­(III), the heme group is highly exposed to the solvent; thus, possibly different mechanisms (probably related to the second step, the ligand exchange reaction) might be operating that lead to the differences observed for the two species.…”

“…This behavior has been previously described in other heme proteins for this ligand and for other ligands, such as hydrogen sulfide or disulfane . Generally, the higher k on observed for the neutral species has been attributed to the facilitated migration from the solvent to the distal cavity. − However, in Mt -Nb­(III), the heme group is highly exposed to the solvent; thus, possibly different mechanisms (probably related to the second step, the ligand exchange reaction) might be operating that lead to the differences observed for the two species. Here, the molecular basis of ONOOH/ONOO – scavenging by Mt -Nb­(III) has been investigated by dissecting the ligand migration toward the active site, the ligand binding process, and the water molecule release by computer simulations.…”

“…The frontier between the QM and MM portions of both systems was treated with the scaled position link atom method . QM/MM methods, particularly the Hybrid package, have proven successful in studying enzymatic reactions involving heme proteins, as previously demonstrated. ,,, …”

“…The total charge of the system was neutralized using Amber’s uniformly charged plasma . Parameters for all residues were taken from the Amber ff19SB force field, except for the ligands (i.e., ONOO – and ONOOH), which were developed using standard protocols, and the heme group, which was the same as those developed from our group that have been shown to provide reliable results in representing the structure and dynamics of the active sites of heme proteins in several studies. ,− Briefly, parameters were calculated from a density functional theory (DFT) calculation using PBE for both the correlation and exchange functionals, developed by Perdew, Burke, and Ernzerhof, and 6-31G** as basis sets. Partial atomic charges were obtained using the restrained electrostatic potential procedure (RESP).…”

Inorganic Polysulfides in Solution: Structural Properties and Conformational Isomerism

“…Application-wise, polysulfides play crucial roles in many biological systems, particularly in oxygen-poor processes. , Oxidation of sulfides proceed during mitochondrial catabolism and in metalloprotein catalyzed processes. − In the process of protein S-sulfhydration (the conversion of cysteinyl thiolates (Cys-S – ) to persulfides (Cys-S-S – )), it has been found that thiol oxidation is mediated by inorganic polysulfides, suggesting that sulfane sulfur rather than sulfide is the actual in vivo agent of H 2 S signaling, as proposed earlier . HS – reacts with NO, and also engages in transnitrosation reactions with nitrosothiolates NOSR, leading to mixtures of S/N hybrid species, inorganic polysulfides and nitroxyl HNO. ,, Sulfides always behave as reductants; the corresponding oxidants reveal a wide range of reactivity, affording moderate rates ( viz ., H 2 O 2 ) up to very fast, almost diffusion controlled, e.g., with HOCl.…”