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PDBsum entry 1mq3
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Transferase/DNA
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PDB id
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1mq3
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of DNA polymerase beta with the mutagenic DNA lesion 8-Oxodeoxyguanine reveals structural insights into its coding potential.
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Authors
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J.M.Krahn,
W.A.Beard,
H.Miller,
A.P.Grollman,
S.H.Wilson.
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Ref.
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Structure, 2003,
11,
121-127.
[DOI no: ]
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PubMed id
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Abstract
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Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG).
During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or
adenine. The ability to accurately replicate through this lesion depends on the
DNA polymerase. We report the first structure of a polymerase with a
promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The
modified guanine residue is in an anti conformation and forms Watson-Crick
hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the
5'-phosphate backbone of the templating nucleotide flips 180 degrees. Thus, the
flexibility of the template sugar-phosphate backbone near the polymerase active
site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our
results provide insights into the mechanisms employed by polymerases to select
the complementary dNTP.
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Figure 3.
Figure 3. DNA Polymerase b Ternary Complex with
8-OxodG-dCTP(A) 2F[o] - F[c] electron density map contoured at 1
s (black), superimposed on the refined model. Additionally, a
difference map was calculated, omitting O8 and contoured at 3.3
s. Negative density (red) is visible at the 8-oxy position of
the template base, demonstrating unbiased evidence of the
presence of the additional oxygen. The ternary complex with an
8-oxodG template base is very similar to the previously
determined ternary complex containing undamaged deoxyguanine
paired with ddCTP [12]. The modified guanine is in the standard
anti conformation, and dCTP is bound with a coordinating Mg2+
atom (data not shown).(B) Comparison of the 5'-phosphate
backbone conformation of 8-oxodG relative to that observed in
the structure of pol b with an unmodified deoxyguanine in the
polymerase active site (orange) [12]. The presence of the sharp
bend along with limited enzyme contacts with this phosphate
enables flipping of the phosphate away from the carbonyl oxygen
at C8 of 8-oxodG. The backbone a torsion angle (O3'-P-O5'-C5')
of the templating guanine is altered 184° when a carbonyl group
is introduced at C8. In addition, the Lys280 side chain
position, but not that of Asp276, is altered in the presence of
8-oxodG.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
121-127)
copyright 2003.
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