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LIFTING THE CURTAIN: USING TOPOLOGY TO PROBE THE HIDDEN ACTION OF ENZYMES 202 Chapter 8â Lifting the Curtain: Using Topology to Probe the Hidden Action of Enzymes De Witt Sumners Florida State University A central problem in molecular biology is understanding the mechanism by which enzymes carry out chemical transformations. The problem is challenging because most experimental techniques provide only a static snapshot, not a moving picture, of the sequence of molecular events that take place inside the catalytic core of the enzyme. For one class of enzymes, however, mathematics provides a powerful tool to the molecular biologist. These enzymes are the ones that perform topological reactions necessary for the winding, unwinding, recombination, and transposition of DNA. Using topological results about knots and tangles, one can peer into the reaction center and infer the mechanisms of action. One of the important issues in molecular biology is the three-dimensional structure (shape) of proteins and deoxyribonucleic acid (DNA) in solution in the cell, and the relationship between structure and function. Ordinarily, protein and DNA structure is determined by X-ray crystallography or electron microscopy. Because of the close packing needed for crystallization and the manipulation required to prepare a specimen for electron microscopy, these methods provide little direct evidence for molecular shape in solution. The three-dimensional shape in solution is of great biological significance but is very difficult to determine (Wang, 1982).