Conversion of arginine to lysine at position 70 of human dihydrofolate reductase: generation of a methotrexate-insensitive mutant enzyme.

@article{Thompson1991ConversionOA,
  title={Conversion of arginine to lysine at position 70 of human dihydrofolate reductase: generation of a methotrexate-insensitive mutant enzyme.},
  author={Paul D. Thompson and J H Freisheim},
  journal={Biochemistry},
  year={1991},
  volume={30 33},
  pages={8124-30}
}
Arginine-70 of human dihydrofolate reductase (hDHFR) is a highly conserved residue which X-ray crystallographic data have shown to interact with the alpha-carboxylate of the terminal L-glutamate moiety of either folic acid or methotrexate (MTX). The rationale for this study was to introduce a conservative amino acid residue change at position 70 (Arg----Lys) which might function as a titratable group and, thus, reveal possible quantitative changes in ligand binding and kinetic parameters as a… CONTINUE READING