Date of Award:

5-2017

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Chemistry and Biochemistry

Department name when degree awarded

Chemistry

Committee Chair(s)

Alvan C. Hengge

Committee

Alvan C. Hengge

Committee

Sean Johnson

Committee

Cheng-Wei Tom Chang

Abstract

Protein-tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphorylated tyrosines by a 2-step mechanism involving nucleophilic attack by cysteine and general acid catalysis by aspartic acid. In most PTPs the aspartic acid resides on a flexible protein loop, consisting of about a dozen residues, called the WPD loop. PTP catalysis rates span several orders of magnitude, and differences in WPD loop dynamics have recently been show to correlate with the rate of enzymatic catalysis. The rate of WPD loop motion could possibly be related to a widely conserved tryptophan residue on the WPD loop. Therefore, point mutants were made in PTP1B (a human PTP) to the conserved tryptophan residue and their effects on catalytic rate and chemical reaction were studied. The results of these studies are presented in this thesis.

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