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PROFILE

Emily Hart,
NSF Graduate Fellow

NSF GK-12 Project: Northeastern University
GK-12-PLUS (Partners Linking Urban Schools)
URL: http://www.gk12.neu.edu

Thesis Title: Defining the Interaction of Carbamoyl Phosphate Synthetase with Glutamine and N-Acetylglutamate
College/University: Northeastern University

Research Advisor: Susan Powers-Lee



Degree Sought
Ph.D.

University Department and/or Lab
Department of Biology

Research Focus
My research focuses on the structure/function relationship of Carbamoyl Phosphate Synthetase.

Description of Research
Carbamoyl phosphate synthetase (CPS) catalyzes the first step in the biosynthesis of pyrimidine nucleotides, arginine and urea. CPSII in Eschericia coli (eCPS) preferentially uses glutamine as the nitrogen donor and has a canonical catalytic triad of residues proposed to hydrolyze glutamine. Mutation of the glutamate (Glu355) member of the triad shows that this residue is not critical for glutamine hydrolysis. I am performing mutation analysis on four conserved residues in the eCPS glutamine amidotransferase domain to determine if one of these residues serves as the third member of a classical triad. Based on the conservation and location of these residues, I anticipate that the other studied residues may be involved in binding glutamine. My hypothesis is that each of the eCPS residues Gln310, Asn311, Asp334 and Gln351 has a significant role in enhancing the cleavage or binding of the glutamine substrate.

CPSI has evolved to use only free ammonia as a nitrogen donor and to require the allosteric activator N ľacetylglutamate (AGA). Although the site of AGA interaction is not defined, it is known that binding of AGA to CPSI leads to a conformational change in which a pair of cysteine sidechains become proximate and can then be selectively induced to undergo disulfide bonding. Only a single pair of proximate sulfhydryl groups is modified upon treatment of the AGA complex of CPSI by a variety of disulfide-inducing reagents and multiple studies have identified one of the cysteine pair as either Cys1327 or Cys1337. I am performing mutation analysis to determine whether Cys1327 and Cys1337 constitute the AGA-responsive pair of cysteine residues in human CPSI (hCPSI) and whether these residues are critical for enzyme activity. My hypothesis for this study is that neither Cys1327 nor Cys1337 is critical for hCPSI activity, but that they do constitute the AGA-responsive pair of cysteine residues.

Example of how my research is integrated into my GK-12 experience
I am assisting four students in the AP Biology class in creating and carrying out a science fair project for the citywide science fair. They are interested in DNA and molecular biology and that is one area that my Ph.D. project focuses on. They specified that they would like to try something forensic, so we have been meeting to try to come up with a project for them.

My years working in molecular biology and biochemistry have also allowed me to assist with questions during labs and bring a real world perspective to units that relate to my research.



Profile date: August 2007
 
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