With this award, the Chemistry of Life Processes program is funding Professor Richard Magliozzo, at Brooklyn College of The City University of New York, to examine the chemical reactions auto-catalyzed by the heme group in catalase-peroxidase that produce an unusual the amino acid adduct cofactor involving covalent attachment of methionine and tryptophan side chains to the phenol ring of a tyrosine. The heme enzyme catalase-peroxidase found in microorganisms and responsible for their protection from harmful oxidative reactions, is an example of an enzyme that contains two cofactors; the well-known heme group (iron-protoporphyrin IX), and also this amino acid adduct. The modification of the polypeptide under study here is unique to catalase-peroxidases and the cofactor structure enables the rapid catalase reaction (2H2O2 = O2 + 2H2O) in an active site designed like that of peroxidases, which generally lack catalase activity. The mechanism for generation of the covalent amino acid adduct is unknown, but expected to involve radicals on the side chains of the tyrosine and tryptophan residues. The principal technique to be applied is electron paramagnetic resonance spectroscopy. The rapid reactions will be probed using rapid mixing techniques to identify the radicals and their evolution in the enzyme isolated under conditions that do not allow formation of the cofactor until samples are prepared for these experiments.

In terms of Broader Impacts, the research in Professor Magliozzo's laboratory will produce an environment for the training of young scientists at the chemistry-biology interface, including high school and undergraduate students. Particularly for the former, exposure to modern scientific research at this early stage will be important, as they begin to formulate their interests and career goals. There are also scientific broader impacts, as this work will provide insight about the unusual post-translational modification chemistry that leads to the formation of this interesting cofactor. Moving forward, the precedents set in this work will position the bioorganic/biophysical chemistry community better to look for other such cofactor adducts in other enzyme active sites.

National Science Foundation (NSF)
Division of Chemistry (CHE)
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David Rockcliffe
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CUNY Brooklyn College
United States
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