An enzyme for urea reveals its structure.

After more than half a century, scientists have finally pinned down the molecular structure of the enzyme urease.

Many bacteria, fungi, and plants -- but not animals -- use urease to break up molecules of urea, commonly found in urine and biological waste, releasing nitrogen-containing compounds. "This finding has agricultural relevance," says P. Andrew Karplus, a biochemist at Cornell University. "Much of the nitrogen in fertilizer comes from urea, which bacteria degrade into ammonia and CO2 using urease."

Knowing the enzyme's structure may make it possible to synthesize urease inhibitors to control the rate of nitrogen release. "That could improve fertilizers," says Karplus, who, along with Cornell chemist Evelyn Jabri and their colleagues, describes the structure in the May 19 Science.

Some urease-secreting bacteria can also infect people. These bacteria seek out the human excretory system, where they thrive and inflame tissues in the urinary tract, kidneys, and stomach. Researchers find these bacteria associated with ulcers, gout, and gallstones, Karplus observes.

"The enzyme's structure is important biomedically because urease inhibitors may be able to stop these invasive bacteria," he says. A potent inhibitor might yield better drugs for treating ulcers or urinary tract infections.

Triggering antibodies to urease might prevent infection, he observes. "Some groups are already looking at possible urease-based vaccines for immunizing people against these bacteria."

Urease has "a long and distinguished history," says Stephen J. Lippard, a chemist at the Massachusetts Institute of Technology. In 1926, urease from jack beans became the first enzyme crystallized in the laboratory. "This accomplishment afforded incontrovertible proof that enzymes were well-defined chemical compounds," Lippard says.

An unusual feature of urease is its dependence on nickel to grab onto and break up urea in the enzyme's active site, Karplus points out. Most similar enzymes rely on zinc to do their handiwork.

Karplus' group isolated urease from the bacterium Klebsiella aerogenes. Using X-ray diffraction, they resolved the enzyme's molecular architecture down to a scale of 2 nanometers. "This fascinating structure," says Lippard, "reveals the intimate details of the molecular geometry at the active site."

With this crystal structure in hand, "an important chapter has ended in the history of enzymology," says Lippard. "For the field of bioinorganic chemistry, however, the structure helps to open new frontiers, one of which is to understand the principles by which [the active site] functions."

Another matter to discern, says Lippard, lies in nickel's various roles in biology. Given that urease appears to be the only enzyme of its type to use nickel, the metal ion's distinctive action remains intriguing, though "uncertain."

Still, observes Lippard, "the crystal structure has clearly revealed the players on the catalytic stage."