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Revealing the workings of 'Mother Nature's blowtorch'
Date:9/14/2007

ANN ARBOR, Mich.---Using atom-level imaging techniques, University of Michigan researchers have revealed important structural details of an enzyme system known as "Mother Nature's blowtorch" for its role in helping the body efficiently break down many drugs and toxins.

The research has been detailed in a series of papers, the most recent published online this month in the journal BBA Biomembranes.

The system involves two proteins that work cooperatively. The first, cytochrome P450, does the actual work, but only when it gets a boost from the second protein, cytochrome b5. To complicate matters, the two proteins can interact only when both are bound to a cell membrane. That makes it difficult to use traditional techniques to discern the structural details that are crucial to the interaction, said Ayyalusamy Ramamoorthy, who leads the research group.

For instance, X-ray crystallography, often used to determine protein structures, requires separating the molecules from their membrane environment. Because part of cytochrome b5 sticks to the membrane, such separations involve breaking the molecule at the sticking point, which happens to be the part that controls its interaction with cytochrome P450. So while crystallography can offer some information on structure, it can't provide insights into exactly what goes on between P450 and b5 during their cozy, membrane-bound encounters, Ramamoorthy said.

However, the technique his lab uses---solid state NMR spectroscopy---can produce detailed images of proteins in the membrane environment, not only revealing molecular structure but also showing how a particular protein nestles into the membrane. Cytochrome b5 presented a challenge even to that versatile method, though, because the molecule has three parts that all behave differently: the rigid, sticky portion that buries into the cell membrane, a highly mobile, water-soluble portion, and a less mobile "linker" that connects the other t
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Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

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