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Mayo Researcher Discovers Target Site for Developing Mosquito Pesticides

Molecular Design Laboratory, studied the genetic makeup of all known acetylcholinesterases in 73 species, including humans. He identified residues that only exist in the mosquito version of the acetylcholinesterase. To identify which of these residues is susceptible to pesticides, he developed a three-dimensional model of mosquito acetylcholinesterase. With this three-dimensional model in hand, Dr. Pang learned how residues function in a way never before possible.

He found that the cysteine and arginine residues were located at the opening of the active site of the mosquito acetylcholinesterase. An active site is a pocket in an enzyme where a fast chemical reaction takes place to break down a molecule or build a new molecule.

Previous studies by Dr. Pang and researchers elsewhere found that the cysteine residue acts as a hook that could tether a small molecule in the active site of an enzyme and permanently damage the enzyme. This led Dr. Pang to believe the cysteine and arginine residues could be targeted by a pesticide that would not affect humans and other mammals.

"While a three-dimensional model of the mosquito enzyme acetylcholinesterase has been reported by other scientists, no mosquito-specific residue at the active site of acetylcholinesterase has been reported until now," Dr. Pang says. "These findings suggest that a chemically stable molecule (to be used as a safer pesticide) could be made to react with the cysteine residue in the mosquito enzyme acetylcholinesterase and irreversibly inhibit the enzyme."

The three-dimensional model Dr. Pang developed was created with a powerful computing system called a terascale system. He built the system with 590 personal computers. Terascale refers to computational power measured in the unit of teraflops, which is a processor capable of a speed of one trillion floating-point operations per second. A single teraflops computer is comparable to a computer that can search at
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