Researchers decode stability blueprint of malaria enzyme

Scientists at Johns Hopkins University have decoded the stability blueprint of an enzyme residing in a parasite cell's membrane, giving them the opportunity to develop drugs to treat parasitic diseases like malaria.

By mapping out the shape and function of the rhomboid protease enzyme of the Plasmodium falciparum parasite, the researchers may be able to create more effective enzyme inhibitors. Rhomboid proteases in the malaria parasite helps the disease to successfully invade red blood cells.

"(It's) the first time we really understand the architectural logic behind the structure of the enzyme," Sinisa Urban, an associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine, said. "These enzymes have no selective inhibitors. We really need to understand how (the enzyme) works - is it as stiff as a rock, or is it more gummy, like Jell-O?"

The researchers determined that the rhomboid enzyme was more Jell-O-like, allowing it to more effectively interact with other proteins it cuts. They then made and tested 150 altered versions of the enzyme to find the four important regions for shape and at least two regions that determine function.

Urban hopes that by understanding these enzymes better, new therapies can be developed to treat malaria and other deadly parasitic diseases.

"We're very excited about our findings and are especially curious about the versions of the enzyme that lost function despite no obvious change in stability or shape," Urban said.