Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein

Hidetoshi Shimokawa, Yoshimitsu Fujii, Masato Furuichi, Mutsuo Sekiguchi, Yusaku Nakabeppu

研究成果: ジャーナルへの寄稿記事

26 引用 (Scopus)

抄録

Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2'-dGTP (8-oxo-dGTP) to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine (8-oxo-G) into nascent DNA. Bacterial and mammalian homologs of MutT protein share the phosphohydrolase module (MutT: Gly37→Gly59). By saturation mutagenesis of conserved residues in the MutT module, four of the 10 conserved residues (Gly37, Gly38, Glu53 and Glu57) were revealed to be essential to suppress spontaneous A:T→C:G transversion mutation in a mutT - mutator strain. For the other six residues (Lys39, Glu44, Thr45, Arg52, Glu56 and Gly59), many positive mutants which can suppress the spontaneous mutation were obtained; however, all of the positive mutants for Glu44 and Arg52 either partially or inefficiently suppressed the mutation, indicating that these two residues are also important for MutT function. Several positive mutants for Lys39, Thr45, Glu56 and Gly59 efficiently decreased the elevated spontaneous mutation rate, as seen with the wild-type, hence, these four residues are non-essential for MutT function. As Lys38 and Glu55 in human MTH1, corresponding to the non-essential residues Lys39 and Glu56 in MutT, could not be replaced by any other residue without loss of function, different structural features between the two modules of MTH1 and MutT proteins are evident.

元の言語英語
ページ(範囲)3240-3249
ページ数10
ジャーナルNucleic acids research
28
発行部数17
出版物ステータス出版済み - 9 1 2000

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Escherichia coli Proteins
Phosphoric Monoester Hydrolases
Mutation
Mutation Rate
Mutagenesis
Proteins
DNA

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein. / Shimokawa, Hidetoshi; Fujii, Yoshimitsu; Furuichi, Masato; Sekiguchi, Mutsuo; Nakabeppu, Yusaku.

:: Nucleic acids research, 巻 28, 番号 17, 01.09.2000, p. 3240-3249.

研究成果: ジャーナルへの寄稿記事

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abstract = "Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2'-dGTP (8-oxo-dGTP) to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine (8-oxo-G) into nascent DNA. Bacterial and mammalian homologs of MutT protein share the phosphohydrolase module (MutT: Gly37→Gly59). By saturation mutagenesis of conserved residues in the MutT module, four of the 10 conserved residues (Gly37, Gly38, Glu53 and Glu57) were revealed to be essential to suppress spontaneous A:T→C:G transversion mutation in a mutT - mutator strain. For the other six residues (Lys39, Glu44, Thr45, Arg52, Glu56 and Gly59), many positive mutants which can suppress the spontaneous mutation were obtained; however, all of the positive mutants for Glu44 and Arg52 either partially or inefficiently suppressed the mutation, indicating that these two residues are also important for MutT function. Several positive mutants for Lys39, Thr45, Glu56 and Gly59 efficiently decreased the elevated spontaneous mutation rate, as seen with the wild-type, hence, these four residues are non-essential for MutT function. As Lys38 and Glu55 in human MTH1, corresponding to the non-essential residues Lys39 and Glu56 in MutT, could not be replaced by any other residue without loss of function, different structural features between the two modules of MTH1 and MutT proteins are evident.",
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AU - Nakabeppu, Yusaku

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