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

9 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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title = "Structure of the Y94F mutant of Escherichia coli thymidylate synthase",

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

Y1 - 2006/9

N2 - 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.

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

Abstract

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