A mechanism for the evolution of protein phosphorylation sites and application towards improving phorylation site prediction
Abstract/Contents
- Abstract
- Protein phosphorylation provides a mechanism for the rapid, reversible control of protein function. Phosphorylation adds negative charge to amino acid side chains, and negatively charged amino acids (Asp/Glu) can sometimes mimic the phosphorylated state of a protein. Using a comparative genomics approach, I show that nature also employs this trick in reverse by evolving serine, threonine, and tyrosine phosphorylation sites from Asp/Glu residues. Structures of three proteins where phosphosites evolved from acidic residues (DNA topoisomerase II, enolase, and C-Raf) show that the relevant acidic residues are present in salt bridges with conserved basic residues, and that phosphorylation has the potential to conditionally restore the salt bridges. The evolution of phosphorylation sites from glutamate and aspartate provides a rationale for why phosphorylation sometimes activates proteins, and helps explain the origins of this important and complex process. After using comparative genomics to uncover the evolutionary origins of phosphorylation, I expanded my work to attempt to predict novel phosphorylation sites using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database of proteins and ortholog families. By examining aligned sites within families of proteins for the trends found in my initial investigation, I sought to improve ways of identifying promising potential phosphorylation sites.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Pearlman, Samuel Mark | |
|---|---|---|
| Associated with | Stanford University, Program in Biomedical Informatics. | |
| Primary advisor | Ferrell, James Ellsworth | |
| Thesis advisor | Ferrell, James Ellsworth | |
| Thesis advisor | Altman, Russ | |
| Thesis advisor | Elias, Joshua | |
| Advisor | Altman, Russ | |
| Advisor | Elias, Joshua |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Samuel Mark Pearlman. |
|---|---|
| Note | Submitted to the Program in Biomedical Informatics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Samuel Mark Pearlman
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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