Structure of the Y94F mutant of Escherichia coli thymidylate synthase

Sue A. Roberts, David C. Hyatt, Jerry E. Honts, Liming Changchien, Gladys F. Maley, Frank Maley, William R. Montfort

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Abstract

Tyr94 of Escherichia coli thymidylate synthase is thought to be involved, either directly or by activation of a water molecule, in the abstraction of a proton from C5 of the 2′-deoxyuridine 5′-monophosphate (dUMP) substrate. Mutation of Tyr94 leads to a 400-fold loss in catalytic activity. The structure of the Y94F mutant has been determined in the native state and as a ternary complex with thymidine 5′-monophosphate (dTMP) and 10-propargyl 5,8-dideazafolate (PDDF). There are no structural changes ascribable to the mutation other than loss of a water molecule hydrogen bonded to the tyrosine OH, which is consistent with a catalytic role for the phenolic OH.

Original languageEnglish (US)
Pages (from-to)840-843
Number of pages4
JournalActa Crystallographica Section F: Structural Biology and Crystallization Communications
Volume62
Issue number9
DOIs
StatePublished - Sep 1 2006

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ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics

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