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PDBsum entry 3a6t
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.6.1.55
- 8-oxo-dGTP diphosphatase.
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Reaction:
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8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H+
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8-oxo-dGTP
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+
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H2O
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=
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8-oxo-dGMP
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+
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diphosphate
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+
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H(+)
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Cofactor:
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Mg(2+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Biol Chem
285:444-452
(2009)
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PubMed id:
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Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base.
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T.Nakamura,
S.Meshitsuka,
S.Kitagawa,
N.Abe,
J.Yamada,
T.Ishino,
H.Nakano,
T.Tsuzuki,
T.Doi,
Y.Kobayashi,
S.Fujii,
M.Sekiguchi,
Y.Yamagata.
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ABSTRACT
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Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP 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 Mn(2+), 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 Odelta (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 to 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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Selected figure(s)
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Figure 2.
Crystal structures of MutT apo and MutT-8-oxo-dGMP complex
forms. A, overall structure of MutT. α-Helices are in pink, and
β-strands are in slate. A missing region of L-A is shown as a
gray dashed line. B, overall structure of MutT-8-oxo-dGMP.
8-Oxo-dGMP is shown in ball and stick representation. C,
comparison of the structures of the apo and complex forms. Apo
and complex forms are shown in gray and slate, respectively. L-A
and L-D regions in MutT-8-oxo-dGMP adopt a closed conformation
as compared with those in the apo form.
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Figure 3.
Recognition of 8-oxo-dGMP by MutT. A, hydrogen bonding
interactions between 8-oxo-dGMP and loop regions (apo in gray
and MutT-8-oxo-dGMP in slate). Amino acid residues involved in
the hydrogen bonding interactions are shown in ball and stick
representation. Water molecules are in red. Hydrogen bonds are
shown as yellow dashed lines. B, the hydrophobic cave composed
of β-1, β-3, β-3′, β-5, and α-2 is represented as a
translucent surface (carbon in white, nitrogen in cyan, and
oxygen in pink). C, interactions for the syn conformation of
8-oxo-dGMP. The hydrogen bond between Oδ of Asn-119 and N7-H of
8-oxoG is shown as a red dashed line. D, van der Waals
interactions around the O8 atom. Amino acid residues recognizing
O8 are shown in ball, stick, and translucent surface. E, a 2F[o]
− F[c] electron density map around 8-oxo-dGMP contoured at 1.5
σ (stereo view).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
285,
444-452)
copyright 2009.
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Figures were
selected
by an automated process.
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Links
