Thermodynamics of Carbon Monoxide Binding by Helical Hemoprotein Models: the Effect of a Competing Intramolecular Ligand

Abstract

Ferrous hemoprotein models 1 and 2 exhibit bis-histidine/mono-histidine coordination equilibrium in aqueous solution. Carbon monoxide binds more tightly to 1 than to 2, a result of stronger Fe(II)–His coordination in 2 arising from interactions between the Trp side chain and the porphyrin ring. Coordination of the more weakly bound histidine ligands to Fe(II) in 1 is shown to be enthalpically favored but entropically disfavored due to the accompanying change in peptide conformation from random coil to α-helix. We demonstrate that competition from the intramolecular His ligand in 1 reduces Δ H° of CO binding compared to the mono-His coordinated form of the compound, an effect which is largely compensated by the positive entropy term due to unwinding of the peptide helix. Trading enthalpic stabilization of an Fe-ligand bond for an entropy gain due to a protein conformational change may be a common mode of action for hemoproteins which function as small molecule sensors.