Biochemistry, Biophysics, and Structural Biology Commons^™

The Role Of Conformational Dynamics In Isocyanide Hydratase Catalysis, Medhanjali Dasgupta

Department of Biochemistry: Dissertations, Theses, and Student Research

Post-translational modification of cysteine residues can regulate protein function and is essential for catalysis by cysteine-dependent enzymes. Covalent modifications neutralize charge on the reactive cysteine thiolate anion and thus alter the active site electrostatic environment. Although a vast number of enzymes rely on cysteine modification for function, precisely how altered structural and electrostatic states of cysteine affect protein dynamics, which in turn, affects catalysis, remains poorly understood.

Here we use X-ray crystallography, computer simulations, site directed mutagenesis and enzyme kinetics to characterize how covalent modification of the active site cysteine residue in the enzyme, isocyanide hydratase (ICH), affects the protein …

Functional Studies Of Human Cellular Detoxification Enzymes, Melanie Neely Willis

Department of Biochemistry: Dissertations, Theses, and Student Research

Cellular detoxification allows for the maintenance of cellular homeostasis and prevention of abnormal cell growth by clearing harmful xenobiotics and endobiotics. After oxygenation by phase I enzymes, phase II enzymes such as glucuronosyltransferases and glutathione-s-transferases conjugate a small molecule to the compound, marking it for subsequent export. Many up-stream enzymes are also essential to cellular detoxification by supplying the small compounds for conjugation. These up-stream enzymes include UDP-glucose dehydrogenase, which synthesizes UDP-glucuronate, and glutamate cysteine ligase, which catalyzes the first and rate-limiting step in the synthesis of glutathione.
UDP-glucose dehydrogenase (UGDH) is an important enzyme in human development and in …