Master of Science
Dr. Martin Stillman
Maintenance of the homeostasis of zinc (Zn) is very important in regulating bodily functions. There are over 300 Zn dependent enzymes identified, where Zn plays a structural or catalytic role. However, excess of Zn in a cell is toxic and free Zn ions are tightly controlled. Metallothioneins (MTs) are small cysteine rich proteins, which can bind up to seven Zn ions and act as a Zn reservoir. The MT2a isoform is predominantly found in the liver. My research focused on the overexpression of human MT2a in Escherichia coli and the investigation of Zn binding pathways of MT2a in vitro. At physiological pH, Zn is terminally bound to the cysteine thiols of MT2a, making bead-like structures (non-cooperative metal binding), while at low pH, Zn formed clusters bridging the terminally bound Zn (cooperative metal binding). These findings draw our attention to investigate how other essential and toxic metals bind to MT2a.
Keywords: Homeostasis, zinc, metallothionein (MT), metallothionein 2a (MT2a), non-cooperative, cooperative, Zn binding pathway
Jayawardena, Devika P., "Expression, Characterization and Metallation Studies of Human Metallothionein Isoform 2a Using Electrospray Ionization Mass Spectrometry" (2017). Electronic Thesis and Dissertation Repository. 4677.