Oxygen Reactivity of the Biferrous Site in the de novo Designed Four Helix Bundle Peptide DFsc: Nature of the “Intermediate” and Reaction Mechanism

• Published in: Journal of the American Chemical Society 2008-07, Vol.130 (29), p.9188-9189
• Main Authors: Calhoun, Jennifer R, Bell, Caleb B, Smith, Thomas J, Thamann, Thomas J, DeGrado, William F, Solomon, Edward I
• Format: Article
• Language: English
• Subjects: Biomimetic Materials - chemistry; Biomimetic Materials - metabolism; Ceruloplasmin - chemistry; Ceruloplasmin - metabolism; Ferric Compounds - chemistry; Ferric Compounds - metabolism; Ferritins - chemistry; Ferritins - metabolism; Ferrous Compounds - chemistry; Ferrous Compounds - metabolism; Kinetics; Nonheme Iron Proteins - chemistry; Nonheme Iron Proteins - metabolism; Oxidation-Reduction; Oxygen - chemistry; Oxygen - metabolism; Phenols - chemistry; Phenols - metabolism; Protein Structure, Secondary; Spectrum Analysis, Raman - methods; Tyrosine - chemistry; Tyrosine - metabolism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja801657y

The DFsc and DFscE11D de novo designed protein scaffolds support biomimetic diiron cofactor sites that react with dioxygen forming a 520 nm “intermediate” species with an apparent pseudo-first-order formation rate constant of 2.2 and 4.8 s−1, respectively. Resonance Raman spectroscopy shows that this absorption feature is due to a phenolate-to-ferric charge transfer transition arising from a single tyrosine residue coordinating terminally to one of the ferric ions in the site. Phenol coordination could provide a proton to promote rapid loss of a putative peroxo species.