Work

Time-Resolved Investigations of Heterobimetallic Cofactor Assembly in R2lox Reveal Distinct Mn/Fe Intermediates

Year: 2017

Type: article

Abstract: The assembly mechanism of the Mn/Fe ligand-binding oxidases (R2lox), a family of proteins that are homologous to the nonheme diiron carboxylate enzymes, has been investigated using time-resolved techniques. Multiple heterobimetallic intermediates that exhibit unique spectral features, including visible absorption bands and exceptionally broad electron paramagnetic resonance signatures, are observed through optical and magnetic resonance spectroscopies. On the basis of comparison to known diiron species and model compounds, the spectra have been attributed to (μ-peroxo)-Mn III /Fe III and high-valent Mn/Fe species. Global spectral analysis coupled with isotopic substitution and kinetic modeling reveals elementary rate constants for the assembly of Mn/Fe R2lox under aerobic conditions. A complete reaction mechanism for cofactor maturation that is consistent with experimental data has been developed. These results suggest that the Mn/Fe cofactor can perform direct C–H bond abstraction, demonstrating the potential for potent chemical reactivity that remains unexplored.

Source: Biochemistry

DOI: 10.1021/acs.biochem.7b00403

Authors: Effie K. Miller, Nicholas E. Trivelas, Pearson T. Maugeri, Elizabeth J. Blaesi, Hannah S. Shafaat

Institutions: Pennsylvania State University, The Ohio State University

Language: English

Topic: Metal-Catalyzed Oxygenation Mechanisms

Subfield: Inorganic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Ohio State University, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases

Awards: Cellular, molecular, and biochemical sciences training grant, Mechanisms of Radical Translocation in Class I Ribonucleotide Reductases, A Systems Biology Approach for Targeted Drug Discovery for Leishmaniasis, G5356207468