Weizmann Institute scientists have developed a method for dynamic documentation of processes occurring in an enzyme during its activity. The method will make it possible to design new synthetic drugs that will target precise targets
"Ideas" - January 2004
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Anyone who has ever made a honey cake and bothered to watch the honey roll and mix in the cake batter, knows that it would not be easy to describe this process in a series of still photographs. The difficulty mainly stems from the need to identify and document the significant fractions of a second in the process, so that the resulting sequence of images will indeed describe the essence of the process.
Scientists who seek to document interaction processes between different molecules (for example, the action of different enzymes on molecules found in their environment), find themselves in a similar situation, although technically more challenging, both due to the tiny size of the molecules and due to the great speed with which they operate.
Prof. Irit Sagi from the Department of Structural Biology at the Weizmann Institute of Science recently developed an original and first of its kind way to deal with this challenge. In an article published in the scientific journal Nature Structural Biology, she describes a method for dynamic documentation of processes and structural changes that occur in an enzyme molecule during its activity. Thanks to the new method, the scientists can watch, for the first time, high-resolution video clips that make it possible to see the movement of individual atoms that change their place in the enzyme molecule.
To produce their video "live," Prof. Sagi and the members of her research group use a technique similar to the stop action photography known in the field of sports broadcasts on television (but carried out on molecular scales). With this method, the process is frozen at certain stages, and advanced methods from the field of chemical analysis are used to determine the exact molecular array that exists at each stage.
Thus, in fact, the scientists succeeded in imposing the supervision regime of Big Brother in the microscopic world of molecules. "This method," says Prof. Sagi, "opens a new window of possibilities in the field of drug development. Now we can accurately identify the active parts of the enzyme molecule, and the structural changes that occur in the molecule during the process in which it operates.
Thanks to the insights that can be obtained in this way, it will be possible to design new synthetic drugs that will be aimed at precise goals, such as influencing the position and activity of a single atom in a molecule."
Prof. Sagi and the members of her research group are currently trying to realize this vision, in a study in which they are developing a medicinal substance designed to inhibit the spread of cancerous tumors in the body. The cancer that tries to spread in the body would have a very hard time doing so, if it weren't for the help of various "traitors" from within the body. One of these potential "traitors" is an enzyme from a family of enzymes called metalloproteinases. This enzyme breaks down the gelatin in the intercellular spaces, and thus breaks through and paves the way for the metastases sent by the cancer cell. Prof. Sagi uses her new tracking technique to monitor the activity of the treacherous enzyme, and based on the tracking findings, to design a special molecule that will curb its destructive activity.
Physics expert
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