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Antibiotics Target a Unique Region of Enzyme

RNA polymerase 'switch region' could be exploited for antibiotic development

FRIDAY, Oct. 17 (HealthDay News) -- The antibiotics myxopyronin, corallopyronin and ripostatin target a unique region of the RNA polymerase (RNAP) enzyme that could be exploited for antibiotic development, researchers report in the Oct. 17 issue of Cell.

Jayanta Mukhopadhyay, Ph.D., from Rutgers University in Piscataway, N.J., and colleagues investigated the region of RNAP, an essential enzyme that transcribes RNA from DNA and is an important antibiotic target, targeted by the antibiotic myxopyronin.

The researchers found that myxopyronin bound to the RNAP "switch region" -- a hinge region that controls the opening and closing of the enzyme's active center -- preventing the interaction of the enzyme with promoter regions. Further experiments showed that this likely occurred by affecting the conformation of the enzyme and preventing transcription initiation. The structurally related antibiotic corallopyronin and the structurally unrelated antibiotic ripostatin also interacted with the switch region, the authors report.

"The RNAP switch region is distant from targets of previously characterized RNAP inhibitors, and, correspondingly, myxopyronin, corallopyronin and ripostatin do not exhibit cross-resistance with previously characterized RNAP inhibitors," Mukhopadhyay and colleagues write. "The RNAP switch region is an attractive target for identification of new broad-spectrum antibacterial therapeutic agents."

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