Research Project
10206443
Advanced Spectroscopic and Computational Analysis of Metal Sites in Enzymes, Biomimetic Models, and Catalytic Intermediates. Summary/Abstract Life of all organisms, including humans, depends on the activation of small stable molecules by metalloproteins to provide selective and rapid chemical transformations. The goal of the proposed research is to elucidate how specific metalloenzymes function by monitoring and analyzing the atomic level changes that occur at the metal active site during the reaction. These studies are augmented with benchmark studies of biomimetic complexes. The understanding gleaned from this work will provide a molecular basis for finding causes and remedies of diseases. The focus of the research efforts will be on how the interfacing of the active sites in metalloproteins with the protein matrix affects enzymatic function. The primary atomic coordination to the metal is of critical importance, but in many cases, weaker secondary sphere interactions, usually hydrogen bonds from nearby amino acid residues can have significant influence as well. The investigations in our lab use advanced spectroscopic and computational methods, providing detailed characterizations of the metal active sites in proteins that can be compared with an extensive database of benchmarks that we and other researchers have gathered from synthetic model complexes over the years. To understand how an enzyme works, we study key steps in their chemical mechanism by trapping and characterizing reactive intermediates and tracking their elemental kinetics on a millisecond time scale. The work is highly collaborative as we depend on the expertise of many synthetic and biochemical research groups to ensure access to biomimetic and protein complexes that can be, through joint effort, prepared cleanly with well-defined protocols.
