Bacterial Cytochrome c Peroxidases: Insight into the Structure‐Function Relationship

Abstract

Understanding how a sequence of amino acids serves as a functional, catalytic unit is a fundamental question in enzymology. The Elliott group studies the structure‐function relationship using bacterial cytochrome c peroxidases (bCCPs) as a model system for probing the interplay between structure, redox chemistry, and catalysis. bCCPs are diheme periplasmic enzymes that reduce hydrogen peroxide to water, requiring two c‐type heme cofactors and two electrons from the cytochrome c pool. Peroxide detoxification is an essential bacterial defense mechanism. A hallmark of bCCPs lies in the potentials of their hemes: a low potential peroxidatic heme (FeL) and a high potential electron transfer heme (FeH). Interestingly, the bCCPs from Shewanella oneidensis (SoCCP) and Nitrosomonas europaea (NeCCP) feature a high sequence identity (60%), yet have key catalytic differences: SoCCP requires reductive activation of FeH, where NeCCP does not. Further, the reduction potentials governing respective FeH are very different: where SoCCP (+245 mV vs NHE) is average for bCCPs, and NeCCP (>400 mV vs NHE) is unusually high. Previous experiments in the Elliott group have found that point mutants in one heme environment can globally affect the redox properties. Specifically, mutating a key glutamate to lysine at FeL, which is expected to directly hinder activity, has unexpectedly altered the reduction potentials of FeH as well as FeL. The high sequence and structural similarities, yet differences in electrochemical properties, present a robust model to probe the influence of nearby residues on redox potentials and to understand bacterial defense mechanisms against damaging oxygen species.