Stereochemistry of a multistep/bipartite methyl transfer reaction: thymidylate synthase.

Atomic structures of thymidylate synthase (TS) reveal key steps in a multi-step reaction and show quantitatively how conformation change is involved in mediating the methyl transfer reaction catalyzed by TS. Numerous alterations in TS produced by mutation, screened by complementation, and further characterized can be understood in terms of the structure and profound structure change required during the TS reaction.