REACTIVITY OF INORGANIC SULFIDE SPECIES TOWARDS A HEME PROTEIN MODEL.

The reactivity of inorganic sulfide species towards heme-peptides was explored under biorelevant conditions, in order to unravel the molecular details of the reactivity of the endogenous hydrogen sulfide towards heme proteins. Unlike ferric porphyrinates, which are reduced by inorganic sulfide, some heme proteins can form stable FeIII-sulfide adducts. In order to isolate protein factors ruling the redox chemistry, we used as system model the undecapeptide microperoxidase (MP11), a heme-peptide derived from cytochrome c proteolysis that retains the proximal histidine bound to the FeIII atom. Upon addition of gaseous hydrogen sulfide (H2S) at pH 6.8, the UV-Vis spectra of MP11 closely resembled those of the low spin ferric-hydroxo complex (only attained at alkaline pH) and cysteine or alkylthiol derivatives, suggesting that the FeIII reduction was prevented. The low frequency region of the resonance Raman spectrum revealed the presence of a FeIII-S band at 366 cm-1, and the general features of a low spin hexacoordinated heme. Sodium sulfide (Na2S) anhydrous was the source of sulfide of choice for the kinetic evaluation of the process. Theoretical calculations showed no distal stabilization mechanisms for bound sulfide species in MP11, highlighting a key role of the proximal histidine for the stabilization of FeIII-sulfide adducts of heme compounds, devoid of distal counterparts, significant for the biochemical reactivity of endogenous hydrogen sulfide.