Thymidylate synthetase - substrate complex formation

Mol Cell Biochem. 1982 Mar 5;43(1):49-57. doi: 10.1007/BF00229539.


The complexes that thymidylate synthetase (TSase) forms with various potent inhibitors have been intensively studied and thoroughly reviewed. Of particular significance is the covalent ternary complex of TSase-FdUMP-5,10-CH2H4PteGlu. FdUMP is the active metabolite of the widely used anti-cancer drug 5-fluorouracil. This complex is thought to be analogous to a steady-state intermediate of the normal enzyme reaction with the substrate dUMP. In this review, we examine the properties of TSase-dUMP complexes in order to determine if there is an experimental basis for drawing a close analogy between dUMP and FdUMP in their interaction with TSase, and also to evaluate data indicating a potential chemotherapeutic value for TSase-dUMP complexes formed in the presence of folate analogs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding, Competitive
  • Chromatography, Gel
  • Deoxyuracil Nucleotides / metabolism*
  • Folic Acid / analogs & derivatives
  • Folic Acid / pharmacology
  • Kinetics
  • Methyltransferases / metabolism*
  • Substrate Specificity
  • Thymidylate Synthase / metabolism*


  • Deoxyuracil Nucleotides
  • Folic Acid
  • Methyltransferases
  • Thymidylate Synthase