Dissertation Defence: MSc Nirman Poudel

Glutathione transferases are important enzymes that play a key role in protecting cells from various threats, including foreign chemicals (xenobiotics). In MSc Nirmal Poudel’s thesis, the crystal structures of four glutathione transferases from different plants and mammals were determined using the technique of X-ray crystallography. The structures revealed in detail the position of important residues involved in the binding and inactivation of xenobiotics. They also revealed changes in the structures during the binding of xenobiotics. The information reported in this thesis will be useful in designing new molecules as enzyme inhibitors to block the activity of glutathione transferases involved in drug and herbicide resistance.

The excessive use of chemicals, such as herbicides and drugs, has led to various forms of resistance by living organisms. In agriculture, the use of herbicides has resulted in the development of weeds that are resistant to herbicides, thus affecting agricultural production. In cancer, the use of chemotherapy leads to the development of resistance against cancer drugs, creating problems in cancer treatment. Both resistance mechanisms have been associated with glutathione transferases. Inhibition of these enzymes could be an effective strategy to overcome these problems.

The design of new enzyme inhibitors requires detailed information of the site where chemicals bind to the enzyme. X-ray crystallography is a highly effective method to obtain the required information. It has been proved crucial in the design of new drugs against various diseases and more recently in the fight against SARS-CoV-2. It uses powerful X-rays which are some 10 trillion times brighter than the X-rays used in routine hospital examinations to analyze crystals of the enzymes and reveal their three-dimensional shape.

The research carried out in this thesis is extremely important and timely, as the prolonged application of herbicides threatens crop production, and the feeding needs of the world population. Besides, the inactivation of cancer drugs during cancer chemotherapy makes treatments inefficient, prolongs suffering and increases the costs. Thus, the development of suitable inhibitors that can efficiently prevent the detoxification properties of glutathione transferases could have significant impact in the well-being of the human population worldwide.

MSc Nirman Poudel will present his thesis on Friday, October 21.

Opponent: Prof. Dr Arwen Pearson (University of Hamburg, Germany)

Custos: Prof. Jyrki Heino (University of Turku, Finland)

Time: Friday, October 21at , 12.15-3.15PM

Place: Pha1 auditorium, Pharmacity, Itäinen Pitkäkatu 4

You can download and read Poudel’s thesis in advance: https://urn.fi/URN:ISBN:978-951-29-8964-5