Thymidylate synthetase - substrate complex formation.

P V Danenberg; A Lockshin

doi:10.1007/bf00229539

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PubMed · 7078549

Thymidylate synthetase - substrate complex formation.

P V Danenberg·A Lockshin

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Abstract

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.

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Binding, Competitive Chromatography, Gel Deoxyuracil Nucleotides Folic Acid Kinetics Methyltransferases Substrate Specificity Thymidylate Synthase Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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P V Danenberg, A Lockshin. 1982-03-05. Thymidylate synthetase - substrate complex formation.. https://doi.org/10.1007/bf00229539

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