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PDBsum entry 3gpy
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References listed in PDB file
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Key reference
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Title
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Encounter and extrusion of an intrahelical lesion by a DNA repair enzyme.
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Authors
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Y.Qi,
M.C.Spong,
K.Nam,
A.Banerjee,
S.Jiralerspong,
M.Karplus,
G.L.Verdine.
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Ref.
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Nature, 2009,
462,
762-766.
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PubMed id
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Abstract
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How living systems detect the presence of genotoxic damage embedded in a
million-fold excess of undamaged DNA is an unresolved question in biology. Here
we have captured and structurally elucidated a base-excision DNA repair enzyme,
MutM, at the stage of initial encounter with a damaged nucleobase, 8-oxoguanine
(oxoG), nested within a DNA duplex. Three structures of intrahelical
oxoG-encounter complexes are compared with sequence-matched structures
containing a normal G base in place of an oxoG lesion. Although the protein-DNA
interfaces in the matched complexes differ by only two atoms-those that
distinguish oxoG from G-their pronounced structural differences indicate that
MutM can detect a lesion in DNA even at the earliest stages of encounter.
All-atom computer simulations show the pathway by which encounter of the enzyme
with the lesion causes extrusion from the DNA duplex, and they elucidate the
critical free energy difference between oxoG and G along the extrusion pathway.
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