RNA polymerase points to new targets for drug design

Researchers at UAB (University of Alabama at Birmingham) have new information on the structure of a key enzyme in bacteria that could lead to improved antibiotics and less antibiotic resistance.

In findings published online in two complementary papers in Nature, the research team describe the differences in an enzyme called RNA polymerase in bacterial cells as opposed to human cells. These differences provide potential new targets for drug design.

“RNA polymerase is the key enzyme regulating the transfer of genetic information from DNA to RNA,” said Dmitry Vassylyev, Ph.D., professor of biochemistry and molecular genetics and lead author of both papers. “All living organisms use this enzyme to transmit the instructions stored in genes (DNA) to messenger RNA (mRNA), which in turn communicates those instructions to the cells.”

Specifically, Vassylyev's team traced the similarities and differences between human RNA polymerase and bacteria RNA polymerase, painting a more complete picture of the structure of this essential enzyme.

“Knowing how RNA polymerase differs in human and bacterial cells means antibiotics can be designed with a greater probability that they will interact with and kill bacteria, while leaving healthy human cells alone,” Vassylyev said.

Vassylyev said that not only does this present a pathway for new antibiotics, it also should allow for existing drugs to be improved. Some antibiotics are very good at killing bacteria, for instance, but have a difficult time penetrating the cell membrane, rendering them fairly ineffective.

Vassylyev's detailed view of RNA polymerase provides a foundation for producing drugs that will efficiently enter cells, bind to the RNA polymerase and destroy bacteria without inhibiting the growth of human cells.

Vassylyev collaborated with Irina Artsimovitch of Ohio State University and Robert Laudick of the University of Wisconsin. The research was funded by the National Institute of General Medicine Sciences, one of the National Institutes of Health.