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PDBsum entry 4g4q
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Hydrolase/DNA
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PDB id
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4g4q
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References listed in PDB file
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Key reference
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Title
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Structural and biochemical analysis of DNA helix invasion by the bacterial 8-Oxoguanine DNA glycosylase mutm.
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Authors
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R.J.Sung,
M.Zhang,
Y.Qi,
G.L.Verdine.
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Ref.
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J Biol Chem, 2013,
288,
10012-10023.
[DOI no: ]
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PubMed id
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Abstract
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MutM is a bacterial DNA glycosylase that serves as the first line of defense
against the highly mutagenic 8-oxoguanine (oxoG) lesion, catalyzing glycosidic
bond cleavage of oxoG to initiate base excision DNA repair. Previous work has
shown that MutM actively interrogates DNA for the presence of an intrahelical
oxoG lesion. This interrogation process involves significant buckling and
bending of the DNA to promote extrusion of oxoG from the duplex. Structural
snapshots have revealed several different highly conserved residues that are
prominently inserted into the duplex in the vicinity of the target oxoG before
and after base extrusion has occurred. However, the roles of these
helix-invading residues during the lesion recognition and base extrusion process
remain unclear. In this study, we set out to probe the function of residues
Phe(114) and Met(77) in oxoG recognition and repair. Here we report a detailed
biochemical and structural characterization of MutM variants containing either a
F114A or M77A mutation, both of which showed significant decreases in the
efficiency of oxoG repair. These data reveal that Met(77) plays an important
role in stabilizing the lesion-extruded conformation of the DNA. Phe(114), on
the other hand, appears to destabilize the intrahelical state of the oxoG
lesion, primarily by buckling the target base pair. We report the observation of
a completely unexpected interaction state, in which the target base pair is
ruptured but remains fully intrahelical; this structure vividly illustrates the
disruptive influence of MutM on the target base pair.
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