Article
The only active mutant of thymidylate synthase D169, a residue far from the site of methyl transfer, demonstrates the exquisite nature of enzyme specificity.
Protein engineering - 1 Mar 2003
Birdsall David L, Finer-Moore Janet, Stroud Robert M
Abstract excerpt
Cysteine is the only variant of D169, a cofactor-binding residue in thymidylate synthase, that shows in vivo activity. The 2.4 A crystal structure of Escherichia coli thymidylate synthase D169C in a complex with dUMP and the antifolate CB3717 shows it to be an asymmetric dimer, with only one active site covalently bonded to dUMP. At the active site with covalently bound substrate, C169 S gamma adopts the roles of...
Topics
- Deoxyuracil Nucleotides
- Dimerization
- Enzyme Stability
- Mutation
- Protein Conformation
- Thymidylate Synthase