Enzymes catalyze otherwise slow reactions with amazing efficiency. Delineating the structural and dynamic features that contribute to enzyme catalytic power is a challenging intellectual exercise in its own right, but also has implications for human health and national security. The Quinn laboratory studies the catalytic mechanisms and inhibition of enzymes of the cholinesterase family. The quintessential enzyme in the family, acetylcholinesterase (AChE), accelerates the hydrolysis of the neurotransmitter acetylcholine by a factor of 1013. The source of this considerable catalytic power is probed by molecular modeling, site-specific mutagenesis, measurement of kinetic isotope effects, and design and evaluation of mechanism-based inhibitors. Moreover, cholinesterases, and AChE in particular, are the targets of organophosphorus nerve agents. Therefore, design of effective antidotes against such agents may be useful in protecting the US against terrorist threats.
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