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Scientists take aim at virulent bacteria by decoding machinery of key control enzyme

e with the wrong methylation pattern, gene expression will be foiled and they will lose their virulence.

"For the first time, using the 3-D crystal structure, we have been able to see the specific Dam structure in action, including the way it binds to the DNA and moves along the base pairs as it recognizes and methylates the A nucleotides," says Dr. Cheng. "Using this information we can potentially design a drug to inhibit this particular enzyme's chemical reaction or its DNA binding process. This kind of rationally designed drug could be an alternative against infections that are resistant to current antibiotics. And because humans don't have Dam methylation, this kind of drug would not interfere with important biological processes in humans."

Other coauthors include Dr. Stanley Hattman, professor of biology from University of Rochester, who cloned and sequenced the Dam gene and has been studying the biochemical mechanism of the enzyme and Dr. Albert Jeltsch and his student Kirsten Liebert from International University Bremen in Germany. Dr. Cheng and his colleagues plan to continue their research using structure-based virtual screening techniques and high throughput equipment to screen for potential inhibitor compounds against the Dam enzyme.


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Source:Emory University Health Sciences Center


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