INOR 82 |
| The use of spectroscopic and computational methods to probe the electronic structures of metalloproteins has led to a significant increase in our understanding of the role of metal-protein interactions in enzyme structure and function. In particular, recent studies have begun to shed light on how Nature activates the unusual Co–C bond of the B12 cofactor 5'-deoxyadenosylcobalamin (AdoCbl) in the AdoCbl-dependent isomerases methylmalonyl-CoA mutase (MMCM) and glutamate mutase (GM). Detailed electronic structure descriptions have been developed for the B12 cofactors and their biologically relevant precursors and are utilized as a framework for interpreting spectral changes observed when these cofactors and cofactor derivatives are bound to the enzyme active sites. These studies have yielded significant insight into the mechanisms by which MMCM and GM activate the AdoCbl cofactor for Co–C bond homolysis and protect the post-homolysis product Co2+Cbl during catalytic turnover. Advances in de novo protein design have also dramatically increased our understanding of metal-protein interactions. Recently, a self-assembling four-helix bundle that contains a di-iron carboxylate active site (DFsc) has been designed that is well-suited for systematic investigations of the structure/function relationships found in natural di-iron carboxylate enzymes as it is easily modifiable via point mutations and it mimics not only the first, but also the second and third, coordination spheres of the natural di-iron cluster. A series of first-shell mutants have been expressed, purified, and characterized to determine their ability to retain a native like fold, bind metal ions (including Fe, Zn, Co, and Mn), and confer catalytic activity. These studies provide insight into the role of the active site residues in directing metal-binding and chemical reactivity in the DFsc scaffold. |
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Young Investigator Symposium
1:30 PM-5:30 PM, Sunday, August 19, 2007 BCEC -- 206 A/B, Oral
Division of Inorganic Chemistry |