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Degree

Master of Science

Program

Biology

Supervisor

Dr. Frederic Marsolais

Abstract

L-asparaginases play an important role in nitrogen mobilization in plants. This study investigated the biochemical and biophysical properties of potassium dependent (PvAspG1) and potassium independent (PvAspG-T2) L-asparaginases from P. vulgaris. Previous studies revealed that PvAspG1 requires potassium for catalytic activation and crystal structure analysis suggested that Ser-118 in the activation loop plays a critical role in alkali metal coordination. This amino acid residue is replaced by an isoleucine in PvAspG-T2. Reciprocal mutants of the enzymes were produced and the effect of the amino acid substitution on the kinetic parameters, secondary structure conformation, allosteric effector binding and pH profile were studied. Introduction of the serine residue conferred potassium dependent activity within PvAspG-T2. Potassium elicited a similar conformational change in PvAspG1 and PvAspG-T2-I117S, as determined by circular dichroism spectroscopy. However, no change in conformation was observed for PvAspG-T2 and PvAspG1-S118I. The presence of the serine residue was associated with a narrow pH profile, with a sharp peak in enzyme activity between pH 6.5-7 and pH 8.0, suggesting that potassium influences the ionization of catalytic residues in the active site. Together, these results indicate that Ser-118 of PvAspG1 is essential and sufficient for potassium activation of plant L-asparaginases.

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Biochemistry Commons

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