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 "Bill" Montfort

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 2006

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Thymidylate Synthase
mutations
Escherichia
Escherichia coli
Thymidine Monophosphate
thymidine
Mutation
Molecules
Water
tyrosine
Thymidine
water
Tyrosine
catalytic activity
Protons
molecules
Hydrogen
Catalyst activity
Chemical activation
activation

ASJC Scopus subject areas

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

Cite this

Structure of the Y94F mutant of Escherichia coli thymidylate synthase. / Roberts, Sue A; Hyatt, David C.; Honts, Jerry E.; Changchien, Liming; Maley, Gladys F.; Maley, Frank; Montfort, William "Bill".

In: Acta Crystallographica Section F: Structural Biology and Crystallization Communications, Vol. 62, No. 9, 09.2006, p. 840-843.

Research output: Contribution to journalArticle

Roberts, Sue A ; Hyatt, David C. ; Honts, Jerry E. ; Changchien, Liming ; Maley, Gladys F. ; Maley, Frank ; Montfort, William "Bill". / Structure of the Y94F mutant of Escherichia coli thymidylate synthase. In: Acta Crystallographica Section F: Structural Biology and Crystallization Communications. 2006 ; Vol. 62, No. 9. pp. 840-843.
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