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SURVIVING IN AN ACID BATH
Crystal structure sheds light on acid resistance of H. pylori urease
MAUREEN ROUHI
The ulcer-causing bacteria called Helicobacter pylori fascinate researchers. These bacteria live in human stomachs, which once were thought uninhabitable because of the extremely acidic conditions they harbor.
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ACID-PROOF The four trimeric assemblies of Helicobacter pylori urease (the fourth, at the back of the figure, is omitted for clarity) cooperatively release ammonia to form a protective neutral layer around the enzyme.
COURTESY OF BYUNG-HA OH |
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H. pylori's survival in the gut is known to be due to its high production of urease. When this enzyme hydrolyzes urea, the ammonia formed neutralizes the acidity around the bacterium, creating a livable microenvironment. Now, the crystal structure of H. pylori urease is providing more clues to the bacteria's survival tactics. The structure was obtained recently by Byung-Ha Oh and coworkers at Pohang University of Science & Technology and at Catholic University of Daegu, both in South Korea [Nat. Struct. Biol., 8, 505 (2001)].
Unlike other ureases, H. pylori urease molecules reside both inside the cytoplasm and on the cell surface. The surface molecules come from spontaneous lysis of other H. pylori, which releases ureases that then adsorb onto the surface of intact bacteria. Scientists have believed that surface urease protects H. pylori against strong acid, but it wasn't clear how. The current work proves that the enzyme survives outside the cell under the usual acidic conditions in the stomach. The Korean researchers credit this survival to the enzyme's architecture.
They find that H. pylori urease has two subunits: a 61.7-kilodalton unit called  and a 26.5-kDa unit called  . Three of each of these subunits form a triangular assembly ()3. Four ()3 trimers assemble into a sphere enclosing a cavity and containing 12 evenly distributed catalytic sites and 10 holes.
Inside the cell, the enzyme's cavity is filled with cell fluid, which has buffering capacity. "That will protect the enzyme temporarily at the time of release," Oh explains. Gradually, the cavity is filled with ammonia as urea in the gastric fluid is hydrolyzed. The 10 holes in the sphere allow diffusion of cell fluid and of ammonia from active sites over the sphere. Shrouded in ammonia, the enzyme, and H. pylori, survives pH 3.
The neutral layer is easily destroyed by vigorous agitation or the presence of a strongly buffered acidic solution, which fits with the view that the enzyme is acid labile. But that view comes from experiments using vigorous agitation or strongly buffered solutions, which would not let pH rise when ammonia is formed. "However, gastric juice is unbuffered, and the enzyme will seldom find itself vigorously floating in the stomach," Oh says. "Therefore, under physiological conditions, the enzyme is acid-stable, largely by virtue of its exquisite molecular design."
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Copyright © 2001 American Chemical Society |
