Time-Resolved Investigations of Heterobimetallic Cofactor Assembly in R2lox Reveal Distinct Mn/Fe Intermediates.
Effie K MillerNicholas E TrivelasPearson T MaugeriElizabeth J BlaesiHannah S ShafaatPublished in: Biochemistry (2017)
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)-MnIII/FeIII 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.
Keyphrases
- metal organic framework
- magnetic resonance
- transition metal
- room temperature
- optical coherence tomography
- aqueous solution
- dna damage
- low density lipoprotein
- mass spectrometry
- high resolution
- risk assessment
- climate change
- dna methylation
- magnetic resonance imaging
- machine learning
- visible light
- ionic liquid
- energy transfer
- high speed
- data analysis
- density functional theory
- clinical evaluation