Spectroscopic studies of molybdenum enzymes

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Molybdenum is the only second-row transition element with a known function in animals. It fulfills functional roles in enzymes in almost all living creatures, from bacteria through plants to invertebrates and mammals. The molybdenum enzymes all contain the metal bound by an unusual sulfur-containing cofactor. Despite possessing common structural elements, the enzymes are remarkable in the range of different chemical reactions that are catalyzed, although almost all are two-electron oxidation-reduction reactions in which an oxygen atom is transferred to or from the molybdenum. The functional roles filled by molybdenum 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 all the major families of molybdenum enzymes using the synchrotron-based technique of X-ray absorption spectroscopy. We propose to use a novel holistic approach in combining information from X-ray absorption spectroscopy, advanced computer molecular modeling, and available protein 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 - X-ray absorption spectroscopy.