Spectroscopic Studies of Molybdenum and Tungsten Enzymes

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Transition metal ions are integral parts of a large number of enzymes, catalyzing many of the most chemically challenging and industrially relevant reactions carried out by living organisms. Among all of the metals employed by living things, molybdenum and tungsten are distinguished as being the only second-row and third-row transition elements with a known function in living creatures; tungsten is further distinguished as the heaviest element used in life. The metals have functional roles in enzymes in almost all living creatures, from bacteria through plants to invertebrates and mammals. They do this within enzyme active sites that all contain the metal bound by an unusual sulfur-containing cofactor. Despite commonality in structure, the enzymes are remarkable in the range of different chemical reactions that are catalyzed, and the functional roles filled by the enzymes are equally diverse; for example, they play essential roles in microbial respiration, in the uptake of nitrogen in green plants, in controlling insect eye color, and in human health. The proposed work is a systematic study of the major families of molybdenum and tungsten enzymes using a combination of synchrotron-based and computational chemistry methods. We propose to use a novel holistic approach in combining information from X-ray absorption spectroscopy, advanced computer molecular modeling, and crystal structures to obtain the most accurate picture yet of the active sites. The ultimate goal of the work is to develop an in-depth quantitative structural and electronic understanding of the catalytic mechanisms used by the enzymes, comparing and contrasting between and within the different families. This will lead to an improved understanding of how molybdenum enzymes achieve their remarkable functional diversity. The benefits of this research are three-fold (i) The results will yield detailed insights for an important group of enzymes (ii) The holistic approach developed will be broadly applicable to all metalloprotein studies (iii) The research will strengthen the Canadian effort in utilizing one of the major synchrotron tools in structural molecular biology.