Quick Dips

Biting the Bugs Back

Imagine being able to plug up the active part of a virus or bacteria before it can "bite" its human host and cause sickness. Research by two Massey University post-doctoral fellows brings this possibility closer than ever before, for one bug.

Dr Jakki Cooney and Dr Todd Kagawa of the Institute of Molecular BioSciences have worked for more than four years to solve the structure of SpeB. This is a proteinase, an enzyme secreted by Streptococcus pyogenes. SpeB produced by the bug degrades or damages proteins essential for the integrity of human cells and tissues.

"It's the cover story. Just getting a paper in PNAS is a milestone for any scientist, but having the paper selected as the cover story is a huge coup" says Professor Pat Sullivan, head of the Institute of Molecular BioSciences.

"There's plenty of incentive to find out how SpeB works," says Sullivan. "With flesh eating disease the only way to stop the disease travelling is to remove the affected tissue. This is not a desirable cure!"

Cooney and Kagawa, who are members of Dr Paul O'Toole's research group, solved the structure of the zymogen form of SpeB. The zymogen form has an extra piece of protein, called a propeptide. When the propeptide is intact, the proteinase, is inactive and harmless. Once the propeptide is removed, SpeB can attack tissues, causing illness.

"You could think of the propeptide as being a plug stopping an attack," Sullivan says.

"Knowing how the plug fits in place opens up all kinds of future research possibilities, but the structure had to be solved and understood before anything more could be done. It's a case of know the enemy."

The next step will be to find out more about how the propeptide works as a natural inhibitor.

Solving SpeB's structure took thousands of hours of patient work, growing tiny crystals under hundreds of different conditions. The best crystals were bombarded with X-rays, in a huge synchrotron machine in France. What was produced looks meaningless to the layperson  --  a film of patterns of dots in different intensities. These were analysed endlessly on a computer to get a focussed image of the structure until one lucky evening, it all came together.

"We could hardly believe it," Cooney says. "We looked at the computer screen and there it was."

Massey University has an international reputation in protein crystallography.

One of the early projects which put Massey "on the map" 20 years ago was the structure of actinidin, the meat-tenderising protein in kiwifruit. Actinidin belongs to the same superfamily of enzymes as SpeB.