Spectroscopic Definition of the Ferroxidase Site in M Ferritin: Comparison of Binuclear Substrate vs Cofactor Active Sites
Autor: | Takehiko Tosha, Edward I. Solomon, Xiaofeng S. Liu, Elizabeth C. Theil, Jennifer K. Schwartz |
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Rok vydání: | 2008 |
Předmět: |
Models
Molecular Circular dichroism Stereochemistry Cooperativity Biochemistry Article Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Nanocapsules Escherichia coli medicine Animals Ferrous Compounds Carboxylate Binding site Binding Sites biology Chemistry Ligand Circular Dichroism Temperature Ceruloplasmin Active site Substrate (chemistry) General Chemistry Models Chemical Apoferritins Ferritins biology.protein Thermodynamics Ferric Anura medicine.drug |
Zdroj: | Journal of the American Chemical Society. 130:9441-9450 |
ISSN: | 1520-5126 0002-7863 |
DOI: | 10.1021/ja801251q |
Popis: | Maxi ferritins, 24 subunit protein nanocages, are essential in humans, plants, bacteria, and other animals for the concentration and storage of iron as hydrated ferric oxide, while minimizing free radical generation or use by pathogens. Formation of the precursors to these ferric oxides is catalyzed at a non-heme biferrous substrate site, which has some parallels with the cofactor sites in other biferrous enzymes. A combination of circular dichroism (CD), magnetic circular dichroism (MCD), and variable-temperature, variable-field MCD (VTVH MCD) has been used to probe Fe(II) binding to the substrate active site in frog M ferritin. These data determined that the active site within each subunit consists of two inequivalent five-coordinate (5C) ferrous centers that are weakly anti-ferromagnetically coupled, consistent with a μ-1,3 carboxylate bridge. The active site ligand set is unusual and likely includes a terminal water bound to each Fe(II) center. The Fe(II) ions bind to the active sites in a concerted manner, and cooperativity among the sites in each subunit is observed, potentially providing a mechanism for the control of ferritin iron loading. Differences in geometric and electronic structure – including a weak ligand field, availability of two water ligands at the biferrous substrate site, and the single carboxylate bridge in ferritin – coincide with the divergent reaction pathways observed between this substrate site and the previously studied cofactor active sites. |
Databáze: | OpenAIRE |
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