The research in this dissertation documents connections between the primary amino acid sequence of proteins, the dynamics of proteins, and their catalytic function. This research project studied two proteins called protein-tyrosine phosphatases (PTPs): the human enzyme PTP1B, and the bacterial enzyme YopH. PTP1B is a human enzyme that down regulates the insulin receptor on the outer cellular membrane, and causes the insulin receptor to be less responsive to insulin. A deeper knowledge of how PTP1B is different from other human PTPs might be useful in designing drugs to increase insulin sensitivity in diabetics. Yersinia Pestis is the bacteria that caused the Black Plague, and YopH is an essential for virulence factor that helps Yersinia Pestis to escape the human immune response.
Using these proteins, the primary sequence of amino acids in a small but critical loop region was altered and the effect on the catalytic efficiency was measured. This research shows how some residues are key to the catalytic efficiency of PTPs while others could be changed with little to no effect on the catalytic efficiency. A deeper understanding of the difference between key residues and structural residues may allow future scientists to create designer enzymes and perhaps design pharmaceuticals that mediate enzyme activity by affecting their protein dynamics.
| Identifer | oai:union.ndltd.org:UTAHS/oai:digitalcommons.usu.edu:etd-8336 |
| Date | 01 August 2018 |
| Creators | Moise, Gwendolyn |
| Publisher | DigitalCommons@USU |
| Source Sets | Utah State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | All Graduate Theses and Dissertations |
| Rights | Copyright for this work is held by the author. Transmission or reproduction of materials protected by copyright beyond that allowed by fair use requires the written permission of the copyright owners. Works not in the public domain cannot be commercially exploited without permission of the copyright owner. Responsibility for any use rests exclusively with the user. For more information contact digitalcommons@usu.edu. |
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