Article
Kinetic studies on drug-resistant variants of Escherichia coli thymidylate synthase: functional effects of amino acid substitutions at residue 4.
Archives of biochemistry and biophysics - 15 Aug 1999
Mahdavian E, Spencer H T, Dunlap R B
Abstract excerpt
A naturally occurring mutant of human thymidylate synthase (hTS) that contains a Tyr to His mutation at residue 33 was found to confer 4-fold resistance to 5-fluoro-2'-deoxyuridine (FdUrd), a prodrug of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). The crystal structure of hTS implicated this Tyr residue in a drug resistance mechanistic role that may include both substrate binding and catalysis (Schiffer et...
Topics
- Bacterial Proteins
- Drug Resistance, Microbial
- Escherichia coli
- Fluorodeoxyuridylate
- Humans
- Kinetics
- Mutation
- Prodrugs
- Protein Conformation
- Substrate Specificity
- Thymidylate Synthase
