Engineered Enzyme Protects against Nerve Gas


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A multidisciplinary team of scientists at the Weizmann Institute of Science succeeded in developing an enzyme that efficiently breaks down certain forms of nerve gas before damage to nerves and muscles can ensue. Their results were published in Nature Chemical Biology.
Agents in the gas disrupt the chemical messages sent between nerve and muscle cells, causing loss of muscle control and ultimately leading to death by suffocation. These substances interfere with the activity of acetylcholinesterase, the enzyme responsible for the breakdown of the chemical messenger – acetylcholine. As a result, acetylcholine continues to exert its effect, resulting in protracted muscle contractions throughout the body. Enzymes had been identified that are able to break down similar nerve agents, but these work inefficiently, making their use impractical.

Prof. Dan Tawfik of the Weizmann Institute’s Biological Chemistry Department and his group developed a special method to induce “natural selection” of enzymes in a test tube, enabling them to engineer tailor-made enzymes. Tawfik showed that this method can improve the efficiency of enzymes by factors of hundreds and even thousands.
The new mutant enzymes have been structurally analyzed by a team of scientists from the Structural Biology Department that included Profs. Joel Sussman and Israel Silman and research student Moshe Ben-David. Further experiments at USAMIRD labs have shown that when these enzymes were given preventively, they afforded animals near-complete protection against two types of nerve agents, even at relatively high exposures.
Prof. Dan Tawfik's research is supported by the Helen and Martin Kimmel Award for Innovative Investigation; the Willner Family Leadership Institute for the Weizmann Institute of Science; the Sassoon and Marjorie Peress Philanthropic Fund; Miel de Botton Aynsley, UK; Yossie Hollander, Israel; and Roberto and Renata Ruhman, Brazil. Prof. Tawfik is the incumbent of the Nella and Leon Benoziyo Professorial Chair.

Prof. Joel Sussman's research is supported by the Jean and Jula Goldwurm Memorial Foundation; the S. & J. Lurje Memorial Foundation; the Nalvyco Trust; Mr. Harold Chefitz, Livingston, NJ; Mr. and Mrs. Yossie Hollander, Israel; Nicolas and Elsa Neuman, Mexico; Dr. Ze'ev Rav-Noy, Los Angeles, CA; the Bruce and Rosalie N. Rosen Family Foundation; and Harry Sussman, Woodbury, NY. Prof. Joel Sussman is the incumbent of the Morton and Gladys Pickman Professorial Chair in Structural Biology.