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PDBsum entry 2van
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References listed in PDB file
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Key reference
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Title
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Mismatched dntp incorporation by DNA polymerase beta does not proceed via globally different conformational pathways.
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Authors
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K.H.Tang,
M.Niebuhr,
C.S.Tung,
H.C.Chan,
C.C.Chou,
M.D.Tsai.
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Ref.
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Nucleic Acids Res, 2008,
36,
2948-2957.
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PubMed id
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Abstract
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Understanding how DNA polymerases control fidelity requires elucidation of the
mechanisms of matched and mismatched dNTP incorporations. Little is known about
the latter because mismatched complexes do not crystallize readily. In this
report, we employed small-angle X-ray scattering (SAXS) and structural modeling
to probe the conformations of different intermediate states of mammalian DNA
polymerase beta (Pol beta) in its wild-type and an error-prone variant, I260Q.
Our structural results indicate that the mismatched ternary complex lies
in-between the open and the closed forms, but more closely resembles the open
form for WT and the closed form for I260Q. On the basis of molecular modeling,
this over-stabilization of mismatched ternary complex of I260Q is likely caused
by formation of a hydrogen bonding network between the side chains of Gln(260),
Tyr(296), Glu(295) and Arg(258), freeing up Asp(192) to coordinate MgdNTP. These
results argue against recent reports suggesting that mismatched dNTP
incorporations follow a conformational path distinctly different from that of
matched dNTP incorporation, or that its conformational closing is a major
contributor to fidelity.
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