How can a single second sphere amino acid substitution cause reduction midpoint potential changes of hundreds of millivolts?

Several possible bases are investigated for the elevated midpoint potential's ([E.sub.m]'s), including altered Fe electronic structure, altered active site electrostatics, altered H-boding and altered redox-coupled proton transfer. The results have shown that the protein matrix can apply very good redox tuning via its influence over redox-coupled proton transfer and the energy associated with it.