Properties of the high-spin heme of MauG are altered by binding of preMADH at the protein surface 40 Å away.

The diheme enzyme MauG catalyzes oxidative post-translational modifications of a protein substrate, precursor protein of methylamine dehydrogenase (preMADH), that binds to the surface of MauG. The high-spin heme iron of MauG is located 40 Å from preMADH. The ferric heme is an equilibrium of five- and six-coordinate states. PreMADH binding increases the proportion of five-coordinate heme three-fold. On reaction of MauG with H2 O2 both hemes become FeIV . In the absence of preMADH the hemes autoreduce to ferric in a multistep process involving multiple electron and proton transfers. Binding of preMADH in the absence of catalysis alters the mechanism of autoreduction of the ferryl heme. Thus, substrate binding alters the environment in the distal heme pocket of the high-spin heme over very long distance.