Standard structural techniques cannot be used. Instead, one must use some kinetic method, such as KIEs. KIEs from substrates labeled at many positions give a highly detailed picture of the TS of an enzyme catalyzed reaction. The TS structure for ricin-catalyzed hydrolysis of an adenylate residue in RNA is shown below. Knowing the TS structure of a reaction is the first step in designing TS mimics as inhibitors.
All organisms possess elaborate DNA repair machinery to maintain the integrity of the genome.
8 oxo G is one of the major products of oxidative DNA damage, e.g. from ionizing radiation. A is often misincorporated at the site of the oxidatively damaged G residue. MutY hydrolyses the adenine base from A in the first step of a multi-step repair process that replaces A with C. Dr. Berti wants to understand how MutY catalyzes this hydrolysis reaction. AroA. Both occur in bacteria and both are antibiotic targets. AroA is part of the biosynthetic pathway for aromatic amino acids.