1. Spectroscopic approaches to elucidating novel iron-sulfur chemistry in the 'radical-Sam' protein superfamily
- Author
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William E. Broderick, Danilo Ortillo, Brian M. Hoffman, Joan B. Broderick, Mbako R. Nnyepi, Charles J. Walsby, and Jian Yang
- Subjects
Iron-Sulfur Proteins ,Free Radicals ,Stereochemistry ,chemistry.chemical_element ,Catalysis ,law.invention ,Inorganic Chemistry ,Spectroscopy, Mossbauer ,law ,Organometallic Compounds ,Moiety ,Physical and Theoretical Chemistry ,Electron paramagnetic resonance ,Nuclear Magnetic Resonance, Biomolecular ,Binding Sites ,Deoxyadenosines ,Chemistry ,Electron Spin Resonance Spectroscopy ,SUPERFAMILY ,Protein superfamily ,Resonance (chemistry) ,Sulfur ,Enzymes ,Enzyme Activation ,Models, Chemical ,Radical SAM - Abstract
Electron paramagnetic resonance (EPR), electron-nuclear double resonance (ENDOR), and Mössbauer spectroscopies and other physical methods have provided important new insights into the radical-SAM superfamily of proteins, which use iron-sulfur clusters and S-adenosylmethionine to initiate H atom abstraction reactions. This remarkable chemistry involves the generation of the extremely reactive 5'-deoxyadenosyl radical, the same radical intermediate utilized in B12-dependent reactions. Although early speculation focused on the possibility of an organometallic intermediate in radical-SAM reactions, current evidence points to novel chemistry involving a site-differentiated [4Fe-4S] cluster. The focus of this forum article is on one member of the radical-SAM superfamily, pyruvate formate-lyase activating enzyme, and how physical methods, primarily EPR and ENDOR spectroscopies, are contributing to our understanding of its structure and mechanism. New ENDOR data supporting coordination of the methionine moiety of SAM to the unique site of the [4Fe-4S]2+/+ cluster are presented.
- Published
- 2005