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

doi:10.1107/S1744309106029691

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

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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 language	English (US)
Pages (from-to)	840-843
Number of pages	4
Journal	Acta Crystallographica Section F: Structural Biology and Crystallization Communications
Volume	62
Issue number	9
DOIs	https://doi.org/10.1107/S1744309106029691
State	Published - Sep 2006

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Genetics
Condensed Matter Physics

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10.1107/S1744309106029691

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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.",

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T1 - Structure of the Y94F mutant of Escherichia coli thymidylate synthase

AU - Roberts, Sue A.

AU - Hyatt, David C.

AU - Honts, Jerry E.

AU - Changchien, Liming

AU - Maley, Gladys F.

AU - Maley, Frank

AU - Montfort, William R.

PY - 2006/9

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AB - 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.

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Structure of the Y94F mutant of Escherichia coli thymidylate synthase

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Y94F mutant of thymidylate synthase bound to thymidine-5'-phosphate and 10-propargyl-5,8-dideazafolid acid

E. coli thymidylate synthase Y94F mutant

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Structure of the Y94F mutant of Escherichia coli thymidylate synthase

Abstract

ASJC Scopus subject areas

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Datasets

Y94F mutant of thymidylate synthase bound to thymidine-5'-phosphate and 10-propargyl-5,8-dideazafolid acid

E. coli thymidylate synthase Y94F mutant

Cite this