Enzyme's "Magic" May Hold Key to Anticancer and Antimicrobial Drugs

Enzyme's "Magic" May Hold Key to Anticancer and Antimicrobial Drugs

by Alisa Zapp Machalek (301) 496-7301
April 29, 1996

"Since the two chains in our model are intertwined, it is essential for them to untwist if they are to separate.... Although it is difficult at the moment to see how these processes occur without everything getting tangled, we do not feel that this objection will be insuperable."

Watson and Crick, 1953

In the seminal paper quoted above, Drs. James D. Watson and Francis H.C. Crick correctly predicted that double-stranded DNA must be locally untwisted to enable gene transcription and chromosome replication. Scientists have known since the 1970s that this biological feat--akin to the familiar magic trick of unlinking two interlocked metal rings--is accomplished by a family of enzymes called topoisomerases.

Their critical role in cell division makes these enzymes prime targets for anticancer drugs. But until recently, scientists couldn't intentionally design such drugs because they knew so little about the enzymes. Now, the inner workings of one topoisomerase have been laid bare by a group of researchers led by NIGMS grantee Dr. James C. Wang, the Mallinckrodt Professor of Biochemistry and Molecular Biology at Harvard University.

In the January 18 issue of Nature, the scientists described the detailed, three-dimensional x-ray structure of yeast topoisomerase II, which is closely related to two forms of topoisomerase II in humans. In the April 30 issue of the Proceedings of the National Academy of Sciences (PNAS), the researchers explain how the yeast enzyme unlinks two int

Contact: Alisa Zapp
NIH/National Institute of General Medical Sciences

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