Grant: Research Tools and Instruments - Category 1 (<$150,000)

Protein X-ray crystallography is the primary technology used for the determination of protein structures at the atomic level. Knowledge of such structures is the starting point for defining and understanding complex biochemical reaction and control mechanisms. This understanding of catalytic and binding processes can then be exploited to tackle the complex processes underlying disease pathways and to devise strategies for combating diseases. The most common example of such strategies is the design of new anti-bacterial and anti-viral drugs based on the likelihood of their binding to specific enzymes or regulatory proteins. In addition, new drugs are being designed that either interfere with or stimulate metabolic pathways within humans and animals to ameliorate aberrant biochemical processes causing disease symptoms. Research in the laboratories of the three applicants is focused on understanding intersubunit signaling linked to catalytic turnover, the design of new anti-bacterial drugs and the study of drug activating and anti-oxidant enzymes. A modern structural biology laboratory focused on protein structure determination combines a number of technologies to integrate the steps from gene isolation through protein expression and purification to protein structure determination. The equipment requested in this application is integral to this strategy and include a viscometer to analyze the light scattering properties, a controlled temperature chamber for crystal growth and a computer network for structural refinement computations.