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Bacterial Cytochrome c Peroxidases: Insight into the Structure‐Function Relationship
Author(s) -
Walsh Kelly,
Sullivan Kristal,
Frato Katherine,
Elliott Sean
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.722.12
Subject(s) - heme , shewanella oneidensis , chemistry , redox , peroxidase , periplasmic space , oxidoreductase , cofactor , cytochrome c , nitrosomonas europaea , cytochrome , cytochrome c peroxidase , electron transport chain , stereochemistry , electron transfer , biochemistry , enzyme , photochemistry , bacteria , biology , inorganic chemistry , nitrite , mitochondrion , escherichia coli , organic chemistry , genetics , gene , nitrate
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 (Fe L ) and a high potential electron transfer heme (Fe H ). 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 Fe H , where NeCCP does not. Further, the reduction potentials governing respective Fe H 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 Fe L , which is expected to directly hinder activity, has unexpectedly altered the reduction potentials of Fe H as well as Fe L . 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.