Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (527K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (16)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Shimokawa, H.
Right arrow Articles by Nakabeppu, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shimokawa, H.
Right arrow Articles by Nakabeppu, Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2000, Vol. 28, No. 17 3240-3249
© 2000 Oxford University Press

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

Hidetoshi Shimokawa1,2, Yoshimitsu Fujii2, Masato Furuichi2,3, Mutsuo Sekiguchi1 and Yusaku Nakabeppu2,3,*

1Department of Biology and Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan, 2Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan and 3CREST, Japan Science and Technology Corporation, Japan

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.

* To whom correspondence should be addressed at: Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan. Tel: +81 92 642 6800; Fax: +81 92 642 6791; Email: yusaku@bioreg.kyushu-u.ac.jp


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
T. Nunoshiba, R. Ishida, M. Sasaki, S. Iwai, Y. Nakabeppu, and K. Yamamoto
A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae
Nucleic Acids Res., October 8, 2004; 32(18): 5339 - 5348.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. Li and A-L. Lu
The C-terminal domain of Escherichia coli MutY is involved in DNA binding and glycosylase activities
Nucleic Acids Res., June 15, 2003; 31(12): 3038 - 3049.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. M. Abdelghany, S. Bailey, G. M. Blackburn, J. B. Rafferty, and A. G. McLennan
Analysis of the Catalytic and Binding Residues of the Diadenosine Tetraphosphate Pyrophosphohydrolase from Caenorhabditis elegans by Site-directed Mutagenesis
J. Biol. Chem., February 7, 2003; 278(7): 4435 - 4439.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. Fujikawa, H. Kamiya, H. Yakushiji, Y. Nakabeppu, and H. Kasai
Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP
Nucleic Acids Res., January 15, 2001; 29(2): 449 - 454.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.