JBIC Journal of Biological Inorganic Chemistry

, Volume 19, Issue 7, pp 1057–1067 | Cite as

Bis-Fe(IV): nature’s sniper for long-range oxidation

  • Jiafeng Geng
  • Ian Davis
  • Fange Liu
  • Aimin LiuEmail author


Iron-dependent enzymes are prevalent in nature and participate in a wide range of biological redox activities. Frequently, high-valence iron intermediates are involved in the catalytic events of iron-dependent enzymes, especially when the activation of peroxide or molecular oxygen is involved. Building on the fundamental framework of iron–oxygen chemistry, these reactive intermediates constantly attract significant attention from the enzymology community. During the past few decades, tremendous efforts from a number of laboratories have been dedicated to the capture and characterization of these intermediates to improve mechanistic understandings. In 2008, an unprecedented bis-Fe(IV) intermediate was reported in a c-type diheme enzyme, MauG, which is involved in the maturation of a tryptophan tryptophylquinone cofactor of methylamine dehydrogenase. This intermediate, although chemically equivalent to well-characterized high-valence iron intermediates, such as compound I, compound ES, and intermediate Q in methane monooxygenase, as well as the hypothetical Fe(V) species in Rieske non-heme oxygenases, is orders of magnitude more stable than these other high-valence species in the absence of its primary substrate. It has recently been discovered that the bis-Fe(IV) intermediate exhibits a unique near-IR absorption feature which has been attributed to a novel charge-resonance phenomenon. This review compares the properties of MauG with structurally related enzymes, summarizes the current knowledge of this new high-valence iron intermediate, including its chemical origin and structural basis, explores the formation and consequences of charge resonance, and recounts the long-range catalytic mechanism in which bis-Fe(IV) participates. Biological strategies for storing oxidizing equivalents with iron ions are also discussed.


High-valent iron Charge resonance Long-range catalysis Radical enzymology Posttranslational modification 



The work in the Liu laboratory at Georgia State University on this project has been supported by National Science Foundation grants MCB-0843537 and CHE-1309942, and the Georgia Research Alliance Distinguished Scientist Program (A.L.). We also acknowledge the Molecular Basis of Disease Area of Focus graduate fellowship support to J.G. and the Center for Diagnostics and Therapeutics fellowship support to F.L..


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Copyright information

© SBIC 2014

Authors and Affiliations

  1. 1.Department of ChemistryGeorgia State UniversityAtlantaUSA

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