Redox potential determination of the Hell’s Gate globin I protein facing multiple exogenous ligands

Hell’s Gate Globin-I from Methylacidiphilum infernorum Displays a Unique Temperature-Independent pH Sensing Mechanism Utililized a Lipid-Induced Conformational Change

“…The effect of oleate on the sixth coordination site of the heme iron is significant for both ferric and ferrous oxidation states. This contrasts with Cygb, where only the ferric form of the protein is affected by oleate binding [ 18 ], but may be related to the unusual ferrous ligand binding observed with HGb-I and ligands like cyanide and imidazole that are more readily observed binding to ferric heme proteins [ 17 ]. Additionally, the lipid binding to ferric Cygb does not cause a shift in the pK for the acid–alkaline transition (His-Fe(III)-His to His-Fe(III)—H 2 O) but eliminates the His-Fe(III)-His form at an acid pH.…”

“…However, the shift in the pK a(obs ) of the heme iron coordination may reflect a pH sensing mechanism, the details of which are at present unknown. The usually low redox potential of HGb-I (unligated −305 mV vs. SHE, Table S1 [ 5 , 18 , 28 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]) and its sensitivity to pH, being more significantly less negative at acidic pH (−191 mV, pH 3.5) [ 17 ], suggests that HGb-I does not act as an oxygen carrier but may act as an electron-transfer catalyst dependent on the FeIII/II redox pair of the heme group [ 17 ]. Acidophiles such as M. infernorum grow optimally at pH 2 to 2.5 [ 6 ].…”

“…Additionally, simulations also suggest a ligand migration pathway resulting in net slower de-oxygenation compared to other globins [ 16 ]. HGb-I exhibits low electrochemical potential with an unusual binding of ligands to the ferrous protein normally only observed with ferric globins [ 17 ].…”