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First look at an enzyme target for antibacterial and cancer drugs
Date:12/20/2007

ey cannot be resealed. The number of damaged DNA strands mount until the cell is destroyed. Because the targeting of these drugs has not been optimal, there have sometimes been side effects that pose their own health risks, including secondary cancers with anti-topoisomerase chemotherapeutics. There also can be issues with the toxicity of antibiotics that target bacterial type II topoisomerases, as well as microbial resistance.

In some respects, its amazing that the anti-topo II drugs have been so effective, said Berger. To the credit of the biochemists and chemists, their discovery and refinement of these compounds have already made a remarkable therapeutic impact. Yet, to best of my knowledge, all of the work on these drugs has been done without a good picture of how type II topoisomerases engage DNA. Our new structural knowledge fills that hole, and should be of significant help for overcoming resistance and for guiding the development of future anti-topo II drugs with improved efficacy.

Berger and his research group are now looking into producing crystallographic images of topo II as it interacts with antibacterial and anticancer drugs to determine what the rules for engagement are.


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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory  
Source:Eurekalert

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