News / Science News |
Scientists Discover Antibiotic Mechanism
NIH | APRIL 22, 2015
The widespread use of antibiotics in modern society has led to a sharp rise in antibiotic-resistant bacteria. As a result, much research has focused on creating new compounds to fight these bacteria.
Borrelidin was isolated from the bacteria Streptomyces about 50 years ago. The compound has broad antibacterial, antifungal, antimalarial, anticancer, insecticidal, and herbicidal activities. It works by interfering with a type of essential enzyme called tRNA synthetase. These enzymes help cells make proteins through a process called translation.
A research team led by Dr. Min Guo of the Scripps Research Institute investigated how borrelidin interferes with threonyl-tRNA synthetase. They used a technique called X-ray crystallography to decipher the structure of the enzyme when borrelidin interacts with it.
The researchers found that borrelidin simultaneously occupies the enzyme binding sites for the amino acid L-threonine, molecule tRNA, and energy molecule ATP. Thus, the compound blocks all 3 molecules from the synthetase’s active site. As a result, L-threonine can’t be linked to its tRNA, and protein translation fails.
The researchers determined that borrelidin binding also causes a change to the structure of the enzyme that creates a fourth spot for borrelidin attachment. Borrelidin inhibits translation by binding to 4 sites that are necessary for threonyl-tRNA synthetase to function.
Researchers have been investigating the potential of tRNA synthetase inhibitors to fight bacteria, fungi, cancers, and autoimmune diseases. The insights from this research may help guide scientists in the rational design of improved, more selective drugs.