Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less