Pandey, Amit Vikram; Henderson, Colin J.; Ishii, Yuji; Kranendonk, Michel; Backes, Wayne L.; Zanger, Ulrich M. (eds.) (2018). Role of Protein-Protein Interactions in Metabolism: Genetics, Structure, Function. Frontiers in Pharmacology. Lausanne: Frontiers Media 10.3389/978-2-88945-385-6
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Genetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks.