Published on June 23, 2009 at 5:30 AM
The current report is the first description of this "tethering" mechanism - named for the fatty lipid that tethers the start of the polymer to the enzyme - in carbohydrate synthesis, Kiessling says, though it may prove to be common among other organisms as well.
In addition to providing insight into what may be a general mechanism for designing and building carbohydrates, the work gives insight into developing new therapeutics against TB. The GlfT2 enzyme is essential for bacterial survival and growth but has never yet been targeted by potential treatment methods. Knowing that the enzyme has two binding sites - one for each end of the growing carbohydrate - makes it an especially appealing candidate.
"Our mechanism provides a blueprint for strategies to block a new anti-mycobacterial target," Kiessling says.
New drug targets will be critical in the fight against tuberculosis, as drug-resistant strains are becoming increasingly widespread. The carbohydrate-synthesizing enzyme represents an untapped and promising resource for crippling even strains that are resistant to current drugs.
The prevalence of carbohydrate polymers in biological systems also means that understanding how their length is controlled has many possible applications, ranging from designing more potent and effective vaccines to facilitating the production of useful fuels from plant materials.
"It's a nice illustration of how basic research can lead to applications that are very practical," says Kiessling.