How do metalloenzymes propagate and control chemical reactions?

Whitney F Kellett, Purdue University


Enzymes control and propagate a dizzying array of chemical reactions, including radical reactions and reactions cleaving carbon-carbon bonds. Metalloenzymes, which contain a metal cofactor, are particularly adept at propagating these reactions. This thesis focuses on several metalloenzymes; each an example of a different unique reaction control strategy. Both experimental and computational methodologies have been employed in order to identify specific residues or features which contribute to each enzyme's ability to control the reaction. Emphasis is made on special properties of the metal Manganese. Controlling residues include not only first shell or active site residues, but also residues more distant from the active-site. Further, manipulation of such residues can be used to alter reactivity at "non"-active-sites, or to alter the apparent electrostatics of the protein (in the case of substitution of hydrogen with fluorine). Electron Paramagnetic Resonance (EPR) and other forms of magnetic spectroscopy can be used to evaluate subtle differences imposed by substitution for controlling residues to a metal center, which gives further insight into the electronic contributions of given residues, as well as the electronic properties of metal cofactors. In summary, the catalysis by Mn-dependent and other metal-dependent metalloenzymes can be investigated through multiple kinetic and spectroscopic avenues, unveiling suprising and novel themes in enzymatic catalysis, such as mechano-chemical switches and super long-distance metallo-interactions.




Nigel, Purdue University.

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