Article
Methotrexate-resistant variants of human dihydrofolate reductase. Effects of Phe31 substitutions.
The Journal of biological chemistry - 1 Apr 1994
Chunduru S K, Cody V, Luft J R, Pangborn W, Appleman J R, Blakley R L
Abstract excerpt
Substitution of glycine or alanine for phenylalanine 31 in human dihydrofolate reductase produces variants that are inhibited less by methotrexate (MTX) than the previously reported serine variant. The 100 times decrease in MTX affinity for the glycine variant is due to slower binding, and to ina...
Topics
- Amino Acid Sequence
- Crystallography, X-Ray
- Drug Resistance
- Enzyme Stability
- Genetic Therapy
- Genetic Variation
- Humans
- Kinetics
- Methotrexate
- Models, Structural
- Models, Theoretical
- Mutagenesis, Site-Directed
- NADP
- Phenylalanine
- Protein Conformation
- Protein Denaturation
- Protein Folding
- Recombinant Proteins