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Towards Understanding Osmolyte Effects On Folate(S) And Dihydrofolate Reductase Proteins, Purva Prashant Bhojane
Towards Understanding Osmolyte Effects On Folate(S) And Dihydrofolate Reductase Proteins, Purva Prashant Bhojane
Doctoral Dissertations
Osmolytes are small molecules that alter water activity and probe role of water in biological processes. Osmotic stress approach explored the role of water in ligand binding to dihydrofolate reductase (DHFR). DHFR catalyzes NADPH dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), which is essential for the synthesis of DNA, amino acids and other metabolic intermediates. R67 DHFR is a plasmid-encoded DHFR that confers resistance against trimethoprim, which is a potent inhibitor of E.coli chromosomal DHFR.
Osmolytes addition decreases the affinity of the substrate towards both the DHFRs. Weak preferential interactions between the osmolytes and DHF impede substrate binding to …