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Vanderbilt University

1. Thompson, Lawrence Casper. Dynamic, Structural, and Mechanistic Study of Glutathione Transferases.

Degree: PhD, Biochemistry, 2006, Vanderbilt University

This project involved the investigation of both the dynamic features of the dimer interface of the Mu class GSH transferase rGSTM1-1, as well as, the structural and mechanistic characteristics of HCCA Isomerase, an enzyme related to the mitochondrial (Kappa) GSH transferase family. The dynamics along the dimer interface of rGSTM1-1 were probed by using site-directed mutagenesis and hydrogen-deuterium exchange mass spectrometry. This work led to hypotheses about the roles of both hydrophobic and electrostatic motifs along the interface. It also resulted in more clear understanding of the regions within each monomer that are important for the stability of individual subunits. Crystallography of HCCA Isomerase in conjunction with activity assays on the native substrates allowed us to conclude that this enzyme is definitely a Kappa GSH transferase. Transient state kinetic measurements with native substrates and analogs as well as crystallography with one of the analogs allowed us to propose a global pathway for HCCA Isomeraseâs catalytic mechanism. Advisors/Committee Members: Richard N Armstrong (chair), Albert H Beth (committee member), Lawrence J Marnett (committee member), Charles R Sanders (committee member), Michael R Waterman (committee member).

Subjects/Keywords: hcca isomerase; hydrogen-deuterium exchange mass spectrometry; glutathione cofactor; isomerization; glutathione binding; mechanistic enzymology; transient state kinetics; crystallography; naphthalene metabolism; Xenobiotics  – Metabolism; phase II enzymes; xenobiotic catabolism; kappa glutathione transferases; dimer stability; Glutathione transferase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Thompson, L. C. (2006). Dynamic, Structural, and Mechanistic Study of Glutathione Transferases. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-06232006-122911/ ;

Chicago Manual of Style (16th Edition):

Thompson, Lawrence Casper. “Dynamic, Structural, and Mechanistic Study of Glutathione Transferases.” 2006. Doctoral Dissertation, Vanderbilt University. Accessed August 09, 2020. http://etd.library.vanderbilt.edu/available/etd-06232006-122911/ ;.

MLA Handbook (7th Edition):

Thompson, Lawrence Casper. “Dynamic, Structural, and Mechanistic Study of Glutathione Transferases.” 2006. Web. 09 Aug 2020.

Vancouver:

Thompson LC. Dynamic, Structural, and Mechanistic Study of Glutathione Transferases. [Internet] [Doctoral dissertation]. Vanderbilt University; 2006. [cited 2020 Aug 09]. Available from: http://etd.library.vanderbilt.edu/available/etd-06232006-122911/ ;.

Council of Science Editors:

Thompson LC. Dynamic, Structural, and Mechanistic Study of Glutathione Transferases. [Doctoral Dissertation]. Vanderbilt University; 2006. Available from: http://etd.library.vanderbilt.edu/available/etd-06232006-122911/ ;

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