Biochemistry, Biophysics, and Structural Biology Commons^™

The In Vivo Effect Of Osmolytes On Folate Metabolism, Timkhite-Kulu Berhane

Masters Theses

Previous studies have found that addition of osmolytes weakens the binding of dihydrofolate (DHF) to R67 dihydrofolate reductase (DHFR), chromosomal DHFR from E. coli and a pteridine reductase. These results support the preferential interaction of DHF with osmolytes compared to water. Thus, a working model where interaction of DHF with osmolytes shifts the binding away from the protein-DHF complex towards the free species was proposed. As tetrahydrofolate and other folate redox states have similar structures to DHF, we predict osmotic stress will lower the catalytic efficiencies of other folate pathway enzymes. In this thesis, we explore the in vivo effects …