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| Name |
Petsko, Gregory A. |
| Location
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Brigham and Women's Hospital |
| Primary Field
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Biophysics and Computational Biology |
| Secondary Field
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Biochemistry |
 Election Citation
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Petsko has developed low temperature methods in protein crystallography and their use to study enzymatic mechanisms. He has pioneered the study of protein dynamics in enzymatic reactions. He has used Laue diffraction to study protein reactions in real-time at atomic resolution, in addition to solving the structure of a number proteins. |
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Research Interests
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For over forty years, I have been trying to understand how enzymes achieve their extraordinary catalytic power. I began by developing X-ray crystallographic methods for direct observation of productive enzyme-substrate and enzyme-intermediate complexes, which led to general techniques for studying protein crystal structures at very low temperatures. I used these methods to obtain atomic-resolution information about several enzyme intermediates. I also discovered that protein flexibility could be studied crystallographically, and mapped the spatial distribution of protein motions as a function of temperature. In collaboration with Professor Dagmar Ringe of Brandeis University, I extended this work, helping develop methods for time-resolved protein crystallography, and finally applied all of these techniques to obtain the first time-lapse pictures, at atomic resolution, of an enzyme (cytochrome P450) in action. In 2003 Dagmar and I completely changed the direction of our joint research program to focus on finding treatments for the major age-related neurodegenerative diseases: Alzheimer's, Parkinson's, and ALS. We took an integrative biology approach that combined structural biology with genetics, biochemistry, and cell biology to identify novel targets and develop novel therapeutics. The first result was a gene therapy for the most common forms of ALS, which is about to be tested in humans. In 2005 we began to collaborate with Dr. Scott Small of Columbia University, a pioneer in anatomical neurobiology who first linked endosomal protein trafficking to neurodegeneration, and together we identified potential small molecule and gene therapies for Alzheimer?s and Parkinson's diseases, which are also nearing human clinical trials. |
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