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Mayo Clinic study could lead to safer pesticides

the anticholinesterase protein sequences of 72 species ranging from humans to chickens and other mammals and pests. He found a cysteine amino acid present in the acetylcholinesterase protein sequences of the greenbug and English grain aphid, but absent in comparable human and animal sequences.

Examining the three-dimensional models of both the greenbug and aphid acetylcholinesterase enzymes with the terascale supercomputer he designed was Dr. Pang's crucial next step. He discovered the pest-specific cysteine residue located at the edge of the active site of the insect acetylcholinesterase.

Acetylcholinesterase enzymes have a deep and narrow active site. A cysteine residue is located at the opening of the active site of insect acetylcholinesterases and can react with a small-molecule pesticide. In other words, the cysteine residue serves as a hook that can tether a small molecule in the active site and damage the enzyme.

However, the cysteine is not present in acetylcholinesterase in humans or animals. So the cysteine residue is essentially a species marker for developing new pesticides that would not harm humans because cysteine is not an enzyme active in humans or mammals, Dr. Pang says.

"We inspected the entire active site of the human enzyme and we couldn't find one cysteine residue," he says.

"It is conceivable that a chemically stable molecule could react with insect-specific cysteine residue and irreversibly inhibit the insect acetylcholinesterases upon binding to the active site. This leads me to believe that the cysteine residue can be used as a species marker for developing a new generation of safer pesticides that can inhibit greenbug and aphid acetylcholinesterase, but not human or animal acetylcholinesterases," Dr. Pang says.

"Protein sequences as one-dimensional information can tell us whether an amino acid we are focusing on is unique, but not whether that amino acid is located in the active sit
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Contact: Amy Reyes
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
12-Oct-2006


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