Gregory A. Petsko

Harvard University

Election Year: 1995
Primary Section: 29, Biophysics and Computational Biology
Secondary Section: 21, Biochemistry
Membership Type: Member

Research Interests

For over twenty-five years, I have been trying to understand how enzymes achieve their extraordinary catalytic power. To understand required determining their appearance. I began by developing crystallographic methods for direct observation of productive enzyme-substrate and enzyme-intermediate complexes which led to techniques for studying protein crystal structures at very low temperatures. We used these methods to obtain high-resolution information about several enzyme intermediates. We discovered that protein flexibility could be studied crystallographically, and we mapped the spatial distribution of protein motions as a function of temperature. In collaboration with Professor Dagmar Ringe of Brandeis University, we extended this work, helping develop methods for time-resolved protein crystallography, and applied them to obtain time-lapse pictures, at atomic resolution, of several enzymes in action. Recently, I have become interested in trying to combine the reductionist approach of biological chemistry with the whole-organism approach of genetics. Therefore, I took sabbatical in Professor Ira Herskowitz's lab at UC San Francisco to learn yeast genetics. In rediscovering the joy of working at the bench with my own hands, I have also found that "the awesome power of yeast genetics" lives up to its billing. In the future, I hope to use genetic as well as biochemical and biophysical tools to study the structure/function relationship as it applies to in vivo as well as in vitro function.

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