Modulating Heme Redox Potential Through Protein-Induced Porphyrin Distortion

摘要

Heme proteins are ubiquitous in biology and are commonly involved in critical processes such as electron transfer, oxidative phosphorylation, and signal transduction. Both the protein environment and the heme cofactor contribute to generate the range of chemical properties needed for these diverse functions. Using the H-NOX (>Heme >Nitric oxide/>OXygen binding) protein from the thermophilic bacterium Thermoanerobacter tengcongensis, we have shown that heme electronic properties can be modulated by porphyrin distortion within the same protein scaffold without changing the heme ligation state or coordination environment. The degree of heme distortion was found to be directly correlated to the electron density at the heme iron, as evidenced by dramatic changes in the heme redox potential and pKa of the distal ligand (⁻OH vs. H2O). Protein-induced porphyrin distortion represents a new strategy to rationally tune the electronic properties of protein-bound porphyrins and could be used to engineer proteins with desired reactivity or functionality.