Breakthrough Research Could Eliminate Dental Disease

A new study has deciphered the structure and functional mechanism of the glucansucrase enzyme that is responsible for dental plaque adhering to teeth.

Researchers at the University of Groningen (The Netherlandsl) analyzed the glucansucrase enzyme from the lactic acid bacterium Lactobacillus reuteri, which uses it to produce α-glucans, a long-chain sugar formed from the splitting of sucrose into glucose and fructose that facilitates the adhesion of the bacteria to the tooth enamel. The researchers then used protein crystallography to elucidate the three dimensional (3D) structure of the fully active, 1,031-residue fragment encompassing the catalytic and C-terminal domains of the enzyme, both in the native state and in complexes with sucrose and maltose.

The crystallography revealed that the folding mechanism of the protein is unique; the various domains of the enzyme are not formed from a single, linear, amino acid chain but from two parts that assemble via a U-shaped structure. Contrary to the current hypothesis, which assumed that the sucrose splitting and glucose addition were performed by different parts of the enzyme, the model revealed that both activities occur in the same active site of the enzyme. This knowledge, according to the researchers, will stimulate the identification of substances that inhibit the enzyme that can be added to toothpaste, mouthwash, or even sweets, making dental caries a thing of the past. The study was published early online on November 30, 2010, in the Proceedings of the [US] National Academy of Sciences (PNAS).

"The various inhibitors studied not only blocked the glucansucrase, but also the digestive enzyme amylase in our saliva, which is needed to degrade starch,” said study coauthor professor Lubbert Dijkhuizen, PhD, of the laboratory of biophysical chemistry. "We already knew that the two enzymes were similar, but the crystal structure revealed that the active sites are virtually identical. Future inhibitors thus need to be directed towards very specific targets because both enzymes are evolutionary closely related.”

Dental plaque is a biofilm, usually colorless, that is formed by colonizing bacteria trying to attach itself to the smooth surface of the tooth. The film is soft enough to come off if scraped with a fingernail. If not removed it starts to harden within 48 hours; in about 10 days the plaque becomes dental calculus (tartar), rock-hard and difficult to remove. Dental plaque can give rise to dental caries, the localized destruction of the tissues of the tooth by acid produced from the degradation of fermentable sugars by Streptococcus mutans, as well as periodontal problems such as gingivitis and periodontitis.

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