CAREER: Experiencing the 5th Dimension, cis/trans and Z/E Isomerizations in Biomolecules

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Proteins are the catalysts of life. For such a catalyst to work, substantial reorganization of the atomic structure of the catalyst itself is required. It would be ideal to follow the catalytic reaction directly from the beginning to the end by looking at all the structures on the atomic length scale and in real time. Time-resolved crystallography is designed to achieve this. This technique is able to record up to 10 billion X-ray structures per second. Time-resolved crystallography is a true kinetic method. It investigates an ensemble of molecules in four dimensions, 3 space dimensions and the time. In order to determine a comprehensive kinetic mechanism, an additional parameter, the temperature, will be varied. Crystallography becomes five-dimensional. This project implements five-dimensional crystallography and uses it to investigate two important biological reactions: the photo-cycle in photoactive yellow protein and the photo-optical switching reaction in a biliprotein. Amongst other things, these investigations will pave the way for example for a rational design of optical switches with new colors that can be used for many applications in biophysical research.Understanding biological catalysis is one of the most important fields in the life sciences. Time-resolved crystallography unifies kinetic with structure determination. With the advent of the world's strongest X-ray sources, the free electron lasers for hard X-rays, five-dimensional crystallography can be brought to utmost perfection in terms of speed and smallness of specimen. This will open new research opportunities. To attract young academics, the PI will introduce macromolecular crystallography to Milwaukee's high schools by training science teachers who work as mentees in the PI's lab. A broad educational program in biophysics at the UW-Milwaukee will attract bright undergraduate and graduate students to be included in ongoing projects. Numerous trips to the world's strongest X-ray sources will give plenty of hands-on opportunities. Results will be distributed through the PI's web page so that anyone can experience the fifth dimension in crystallography.