Abstract
Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, an event that can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate specificity for 8-oxoguanine nucleotides; however, the structural basis for this specificity is unknown. The crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn2+, respectively, were determined. MutT strictly recognizes the overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This recognition mode revealed that 8-oxoguanine nucleotides are discriminated from guanine nucleotides by not only the hydrogen bond between the N7-H and Oδ (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine nucleotides prefer. Nevertheless, these discrimination factors cannot by themselves explain the roughly 34,000-fold difference between the affinity of MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is compared with the ligand-free form, ordering and considerable movement of the flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change.
| Original language | English |
|---|---|
| Pages (from-to) | 444-452 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 285 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2010 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. / Nakamura, Teruya; Meshitsuka, Sachiko; Kitagawa, Seiju; Abe, Nanase; Yamada, Junichi; Ishino, Tetsuya; Nakano, Hiroaki; Tsuzuki, Teruhisa; Doi, Takefumi; Kobayashi, Yuji; Fujii, Satoshi; Sejiguchi, Mutsuo; Yamagata, Yuriko.
In: Journal of Biological Chemistry, Vol. 285, No. 1, 01.01.2010, p. 444-452.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base
AU - Nakamura, Teruya
AU - Meshitsuka, Sachiko
AU - Kitagawa, Seiju
AU - Abe, Nanase
AU - Yamada, Junichi
AU - Ishino, Tetsuya
AU - Nakano, Hiroaki
AU - Tsuzuki, Teruhisa
AU - Doi, Takefumi
AU - Kobayashi, Yuji
AU - Fujii, Satoshi
AU - Sejiguchi, Mutsuo
AU - Yamagata, Yuriko
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, an event that can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate specificity for 8-oxoguanine nucleotides; however, the structural basis for this specificity is unknown. The crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn2+, respectively, were determined. MutT strictly recognizes the overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This recognition mode revealed that 8-oxoguanine nucleotides are discriminated from guanine nucleotides by not only the hydrogen bond between the N7-H and Oδ (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine nucleotides prefer. Nevertheless, these discrimination factors cannot by themselves explain the roughly 34,000-fold difference between the affinity of MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is compared with the ligand-free form, ordering and considerable movement of the flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change.
AB - Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, an event that can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate specificity for 8-oxoguanine nucleotides; however, the structural basis for this specificity is unknown. The crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn2+, respectively, were determined. MutT strictly recognizes the overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This recognition mode revealed that 8-oxoguanine nucleotides are discriminated from guanine nucleotides by not only the hydrogen bond between the N7-H and Oδ (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine nucleotides prefer. Nevertheless, these discrimination factors cannot by themselves explain the roughly 34,000-fold difference between the affinity of MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is compared with the ligand-free form, ordering and considerable movement of the flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change.
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UR - http://www.scopus.com/inward/citedby.url?scp=73649095513&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.066373
DO - 10.1074/jbc.M109.066373
M3 - Article
C2 - 19864691
AN - SCOPUS:73649095513
VL - 285
SP - 444
EP - 452
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 1
ER -