Carnegie Mellon

The Hendrich Metalloprotein Group

Biophysical Chemistry   •   Enzymatic Mechanisms   •   Spectroscopy   •   Bioinorganic Chemistry

Approximately one-third of the proteins in the human body contain metals. These and other metalloproteins are essential for the basic processes of life, including DNA synthesis, metabolism, photosynthesis, detoxification, and the chemical transformations of nitrogen, oxygen, and carbon molecules required for life. Many diseases are due to metal imbalances or inactivity of critical metalloenzymes. Furthermore, metalloenzymes are nature’s amazingly efficient and selective nano-materials for catalytic transformation of the most stable chemical bonds in nature, and thus are important factors for health, agriculture, and the environment. An understanding of the function of metalloproteins comes from both structural and spectroscopic studies of the chemical states of the metal centers when processing substrates. Our focus is on molecular level spectroscopic studies of the metal sites and its surrounding ligands. In addition, we collaborate with many groups that synthesize novel metal complexes that model some aspect of the chemistry of metalloenzymes. The metals of interest (V, Cr, Mn, Fe, Co, Ni, Cu, Mo) have unpaired electrons which we probed with EPR, ENDOR, Mössbauer spectroscopies, or SQUID magnetization. An understanding of catalytic function is achieved through isolation and characterization of intermediates of reaction cycles of enzymes and biomimetic complexes. We have developed new spectroscopic instrumentation, computer simulation software, and quantitative methodologies specifically suited to probe metalloproteins and metal complexes.

Many metalloproteins are amazing and intricate complexes with multiple metal cofactors having different functions. Two larger complexes under current study in the group are the b6f complex of oxygenic photosynthesis and a new class of multiheme enzymes important in metabolic functions. Manganese proteins and enzymes and Mn-nucleic interactions are important in a diverse range of biological functions. Compared to our knowledge of Fe and Cu systems, relatively little is understood regarding Mn proteins, and the mechanisms by which Mn can affect human health are only now beginning to be unraveled. Our advances EPR spectroscopy now allow an unprecedented ability to quantitatively characterize the active Mn sites of proteins and enzymes. Insight into the structure/function relationship of proteins and their chemical mechanism will be derived from detailed spectroscopic studies of the proteins, substrate/inhibitor complexes, and catalytic intermediates.