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Is it a rock, or is it Jell-O? Defining the architecture of rhomboid enzymes
Date:8/2/2012

Johns Hopkins scientists have decoded for the first time the "stability blueprint" of an enzyme that resides in a cell's membrane, mapping which parts of the enzyme are important for its shape and function. These studies, published in advance online on June 14 in Structure and on July 15 in Nature Chemical Biology, could eventually lead to the development of drugs to treat malaria and other parasitic diseases.

"[It's] the first time we really understand the architectural logic behind the structure of the enzyme," says Sinisa Urban, Ph.D., an associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine and an investigator at the Howard Hughes Medical Institute, who with his team has unlocked the mysteries of a special class of enzymes called rhomboid proteases.

Rhomboid proteases are present in many different organisms, and are a unique type of enzyme that resides in the cell's membrane where they cut proteins. Previously Urban and his colleagues demonstrated that the rhomboid enzyme is critical for Plasmodium falciparum, the parasite that causes malaria, to successfully invade red blood cells, a step that ultimately leads to infection. Urban says understanding the stability of rhomboid protease shape may impact the design of enzyme inhibitors potential drugs. "These enzymes have no selective inhibitors," says Urban. "We really need to understand how [the enzyme] works is it as stiff as a rock, or is it more gummy, like Jell-O?"

One challenge of studying rhomboid enzymes is that they are surrounded by membranes, making them more difficult to manipulate and work with. To address this, Urban's research team turned to a technique known as thermal light scattering, which heats enzyme samples to progressively higher temperatures while measuring the amount of light bouncing back off of the molecules. Enzymes that have broken from their normal shape will scatter light different
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Contact: Vanessa McMains
vmcmain1@jhmi.edu
410-502-9410
Johns Hopkins Medical Institutions
Source:Eurekalert  

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