Although NMR methods are routinely used to "take molecular pictures" of small proteins, large proteins – and particularly those that reside within the cell membrane – have been reluctant to smile for the camera.
Charles Sanders, Ph.D., professor of Biochemistry, and colleagues have determined the NMR structure of the large bacterial protein diacylglycerol kinase (DAGK), a complex of three subunits that each cross the membrane three times (for a total of nine membrane spans).
The group's ability to identify the NMR structure of DAGK suggests that similar methods can now be used to study the structures of other membrane proteins.
"We're taking the methods that we used for diacylglycerol kinase and applying them to high value targets such as G protein-coupled receptors," Sanders said.
G protein-coupled receptors – the largest family of cell signaling proteins – are targets for about half of all pharmaceuticals. Sanders is collaborating with other Vanderbilt investigators to tackle G protein-coupled receptor structure using both NMR and a complementary structural approach, X-ray crystallography.
DAGK may be a therapeutic target for certain types of bacterial infections. It is a virulence factor in the bacteria Streptococcus mutans, which causes tooth decay.
COMPAMED.de; Source: Vanderbilt Medical Center