Summary information and primary citation
- PDB-id
-
5kn9;
DSSR-derived features in text and
JSON formats
- Class
- hydrolase-DNA
- Method
- X-ray (1.93 Å)
- Summary
- Muty n-terminal domain in complex with DNA containing
an intrahelical oxog:a base-pair
- Reference
-
Wang L, Chakravarthy S, Verdine GL (2017): "Structural
Basis for the Lesion-scanning Mechanism of the MutY DNA
Glycosylase." J. Biol. Chem.,
292, 5007-5017. doi: 10.1074/jbc.M116.757039.
- Abstract
- The highly mutagenic A:8-oxoguanine (oxoG) base pair is
generated mainly by misreplication of the C:oxoG base pair,
the oxidation product of the C:G base pair. The A:oxoG base
pair is particularly insidious because neither base in it
carries faithful information to direct the repair of the
other. The bacterial MutY (MUTYH in humans) adenine DNA
glycosylase is able to initiate the repair of A:oxoG by
selectively cleaving the A base from the A:oxoG base pair.
The difference between faithful repair and wreaking
mutagenic havoc on the genome lies in the accurate
discrimination between two structurally similar base pairs:
A:oxoG and A:T. Here we present two crystal structures of
the MutY N-terminal domain in complex with either undamaged
DNA or DNA containing an intrahelical lesion. These
structures have captured for the first time a DNA
glycosylase scanning the genome for a damaged base in the
very first stage of lesion recognition and the base
extrusion pathway. The mode of interaction observed here
has suggested a common lesion-scanning mechanism across the
entire helix-hairpin-helix superfamily to which MutY
belongs. In addition, small angle X-ray scattering studies
together with accompanying biochemical assays have
suggested a possible role played by the C-terminal
oxoG-recognition domain of MutY in lesion scanning.
