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Closing in on an ulcer- and cancer-causing bacterium
Date:12/7/2011

ist within the acid bath in the human stomach that has made it such a successful, albeit harmful, vector, says Fong. "The key is its use of an enzyme called urease to neutralize gastric acid," he explains.

H. pylori produce urease to spur the breakdown of urea, a naturally occurring chemical in the body, so that urea can release ammonia and make the gut an environment in which the pathogens can thrive. But, unlike most other enzymes, urease doesn't start doing its job immediately after being produced by the bacterium; instead, two nickel ions have to be delivered to it, and then the enzyme can mature, so to speak, and thus allow H. pylori to begin their damaging work.

"As the survival of H. pylori depends on active urease, this is a life-or-death issue for the pathogen to ensure nickel ions are delivered to the urease," says Kam-Bo Wong, a professor who oversaw the project at the institution.

It's not entirely clear how H. pylori make sure that urease can mature and then neutralize the surrounding acid. But Wong's team focused on four proteins that they suspect are helpers: UreE, UreF, UreG and UreH.

Using X-ray crystallography, "which essentially performs the function of a molecular microscope to visualize proteins with atomic resolution," Fong explains, the team took snapshots of UreF and UreH. What they saw was that UreH morphs the shape of UreF to enable UreF to recruit a third player, UreG, to form the UreF-UreH-UreG complex. In other words, the three proteins hook up to collectively deliver nickel ions to the right place on urease. Once the nickel ions are in place, they serve like a flint to ignite the breakdown of urea into ammonia, which then neutralizes the stomach acids.

"So, now we have a better understanding of how the machine can assemble itself, as if a skillful mechanic were there for the job, and deliver the nickel ions," says Fong.

Importantly, the team also discovered
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Contact: Angela Hopp
ahopp@asbmb.org
240-283-6614
American Society for Biochemistry and Molecular Biology
Source:Eurekalert  

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