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.