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| Home > Facutly > Susan Powers-Lee | |||||||||||||||||||||||||||||||
Susan
Powers-Lee Ph.D., University of California, Berkeley Research
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Email: s.powers-lee@neu.edu Phone:
617.373.2385 Location:
134 Mugar Life Sciences |
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Research Description My lab studies how protein structures have evolved to catalyze unique enzymatic activities, and to participate in a diverse set of intracellular communications. Our present studies are focused on human detoxification of ammonia and its control mechanisms. Carbamoyl phosphate synthetase (CPS), which catalyzes the entry and regulated step of the urea cycle, is known to be the primary site of ammonia detoxification. Future research studies are aimed at using structural, biochemical, molecular and bioinformatics techniques to define the structure and function of human CPS and to relate these parameters to those of potential evolutionary relatives.
Sketch of the bacterial CPS tetramer, showing the functional domains of one monomeric unit in different colors. We are using this structure as a template to model other CPSs while simultaneously carrying out collaborative studies to obtain X-ray structures for mammalian CPSs. We are also reverse engineering various CPSs by creating site-directed mutants, truncated constructions and chimeras. An additional major goal is elucidation of the intramitochondrial environment for CPS and its effect on the enzyme's structure and function. Applications of these studies include developing treatments for hepatitis and other disorders in which liver function is temporarily or permanently altered.
Kothe, M., Purcarea, C., Guy, H. I., Evans, D. R., and Powers-Lee, S. G., "Direct Demonstration of Carbamoyl Phosphate Formation on the C-terminal Domain of Carbamoyl Phosphate Synthetase," Protein Science, 14, 37-44 (2005).
Saeed-Kothe, A., and Powers-Lee, S.G. "Gain of Glutamine Function in an Ammonia Specific Carbamoyl Phosphate Synthetase," J. Biol. Chem. 278, 26722-26726 (2003). Eroglu,
B., and Powers-Lee, S.G., "Unmasking a Functional
Allosteric Domain in an Allosterically Nonresponsive Carbamoyl Phosphate
Synthetase," J. Biol. Chem. 277, 45466-45472 (2002).
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