Dynamics, Catalysis, and Residue Networks within a Phosphohexomutase

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Intellectual meritEnzymes are responsible for the many chemical reactions that allow life to occur. To really understand how enzymes work, both their three-dimensional shapes and the molecular motions that they undergo must be studied. New information suggests that protein structure and movements are connected in a very complex fashion, via "pathways" of amino acid residues. This important issue will be studied in an enzyme from the bacterium P. aeruginosa. This enzyme (called phosphomannomutase/phosphoglucomutase or PMM/PGM) helps the bacteria produce polysaccharides and other sugar-containing products. Because its three-dimensional structure has already been carefully studied, it is an excellent system for investigating the complicated question of how structure and movements are related. In particular, the project involves use of biophysical techniques, including nuclear magnetic resonance, to create a detailed picture of the molecular movements and fluctuations that permit the enzyme to perform its catalytic reaction. These studies will help find the hidden pathways of amino acids involved in these processes. Understanding these pathways may eventually help researchers design new types of proteins, such as faster and more efficient enzymes, that can be used in industry or medicine. Broader ImpactThese studies are at the interface of structural biology, enzymology, and computational biology. Both undergraduate and graduate students will participate in this work and gain valuable experience in this emerging, interdisciplinary area. Special emphasis for training opportunities will be given to women and minority students. In addition, parts of the experimental studies will be incorporated into the graduate level curriculum in the Biochemistry department, allowing many students to gain insights into these important issues.