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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.

SUBMITTER: Roberts SA

PROVIDER: S-EPMC2242863 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Structure of the Y94F mutant of Escherichia coli thymidylate synthase.

Roberts Sue A SA Hyatt David C DC Honts Jerry E JE Changchien Liming L Maley Gladys F GF Maley Frank F Montfort William R WR

Acta crystallographica. Section F, Structural biology and crystallization communications 20060818 Pt 9

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 chang ...[more]

PMID: 16946460

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