DOI
https://doi.org/10.25772/8F0P-KH63
Author ORCID Identifier
0000-0003-2212-3741
Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Integrative Life Sciences
First Advisor
Peter Uetz
Second Advisor
Stephen Fong
Abstract
Proteins bind other proteins and work together as machines to perform many biological functions. Metabolic enzymes governing the life-sustaining metabolic reactions and therefore, metabolism are proteins which also binds other proteins. In this dissertation work, I have explored proteins when they interact with metabolic enzymes, play any role in regulating the cell’s metabolism. I study this phenomenon in Escherichia coli whose protein-protein interaction data is readily available in public databases with proper reference to the experimental study. Another good reason is the predictions we make in this computational study can be tested and validated in E. coli as it is a commonly used model organism in biology wet lab experiments. Not all metabolic enzymes bind proteins and if they do, not all interactions will play metabolic regulation roles but to identify the ones where this can happen is one of the main objectives of this dissertation study. We can’t identify protein-enzyme interactions (PEIs) at random among many playing metabolic regulations, but it is only possible by understanding how proteins bind enzymes in metabolic regulation contexts at a comprehensive scale. We do this by large-scale visualization of the interface of protein-protein interaction networks and metabolic pathways. Once I obtained the experimentally published protein-enzyme interaction data of E. coli, what are the characteristics of interactors (proteins binding metabolic enzymes), in what amounts protein and enzyme bind during a metabolic state and how much they co-occur in different species are some of the analyses I have done in this dissertation to comprehend the metabolic regulation functions of protein-enzyme interactions. Finally, we were able to propose some novel E. coli protein-enzyme interactions as metabolism regulators, some of which are backed up by literature. Also, we have found many unknown proteins binding metabolic enzymes in a wide range of bacteria including pathogens and microbiome species which if explored in a wet lab can give us insights to new metabolic (or non-metabolic) functions occurring at the protein interaction level.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-10-2024