HS/Thiols, NO, and NO/HNO: Interactions with Iron Porphyrins.

In the past decade, gasotransmitters NO and HS have been thoroughly studied in biological contexts, as their biosynthesis and physiological effects became known. Moreover, an additional intricate reaction scheme between these compounds and related species is thought to exist as part of the cascade signaling processes in physiological conditions. In this context, heme enzymes, as modeled by iron porphyrins, play a central role in catalyzing the key interconversions involved.

Reactivity of inorganic sulfide species towards a pentacoordinated heme model system.

The reactivity of inorganic sulfide towards ferric bis(N-acetyl)- microperoxidase 11 in sodium dodecyl sulfate has been explored by means of visible absorption and resonance Raman spectroscopies. The reaction has been previously studied in buffered solutions at neutral pH and in the presence of excess sulfide, revealing the formation of a moderately stable hexacoordinated low spin ferric sulfide complex that yields the ferrous form in the hour's timescale. In the surfactant solution, instead, the ferrous form is rapidly formed.

Hemeproteins as Targets for Sulfide Species.

Sulfides are endogenous and ubiquitous signaling species that share the hemeproteins as biochemical targets with O, nitric oxide, and carbon monoxide. The description of the binding mechanisms is mandatory to anticipate the biochemical relevance of the interaction. The binding of sulfide to ferric hemeproteins has been described in more than 40 systems, including native proteins, mutants, and model systems.

Mechanism of Sulfide Binding by Ferric Hemeproteins.

The reaction of hydrogen sulfide (HS) with hemeproteins is a key physiological reaction; still, its mechanism and implications are not completely understood. In this work, we propose a combination of experimental and theoretical tools to shed light on the reaction in model system microperoxidase 11 (MP11-Fe) and myoglobin (Mb-Fe), from the estimation of the intrinsic binding constants of the species HS and hydrosulfide (HS), and the computational description of the overall binding process. Our results show that HS and HS are the main reactive species in Mb-Fe and MP11-Fe, respectively, and that the magnitude of their intrinsic binding constants are similar to most of the binding constants reported so far for hemeproteins systems and model compounds.

Reactivity of inorganic sulfide species toward a heme protein model.

The reactivity of inorganic sulfide species toward heme peptides was explored under biorelevant conditions in order to unravel the molecular details of the reactivity of the endogenous hydrogen sulfide toward heme proteins. Unlike ferric porphyrinates, which are reduced by inorganic sulfide, some heme proteins can form stable Fe(III)-sulfide adducts. To isolate the protein factors ruling the redox chemistry, we used as a system model, the undecapeptide microperoxidase (MP11), a heme peptide derived from cytochrome c proteolysis that retains the proximal histidine bound to the Fe(III) atom.