Summary information and primary citation
- PDB-id
-
8th9;
DSSR-derived features in text and
JSON formats
- Class
- lyase
- Method
- X-ray (2.08 Å)
- Summary
- Structure of mammalian neil2 from monodelphis domestica
in complex with thf-containing DNA
- Reference
-
Eckenroth BE, Bumgarner JD, Matsumoto-Elliott O, David
SS, Doublie S (2023): "Structural
and biochemical insights into NEIL2's preference for
abasic sites." Nucleic Acids Res.,
51, 12508-12521. doi: 10.1093/nar/gkad1075.
- Abstract
- Cellular DNA is subject to damage from a multitude of
sources and repair or bypass of sites of damage utilize an
array of context or cell cycle dependent systems. The
recognition and removal of oxidatively damaged bases is the
task of DNA glycosylases from the base excision repair
pathway utilizing two structural families that excise base
lesions in a wide range of DNA contexts including duplex,
single-stranded and bubble structures arising during
transcription. The mammalian NEIL2 glycosylase of the
Fpg/Nei family excises lesions from each of these DNA
contexts favoring the latter two with a preference for
oxidized cytosine products and abasic sites. We have
determined the first liganded crystal structure of
mammalian NEIL2 in complex with an abasic site analog
containing DNA duplex at 2.08 Å resolution. Comparison to
the unliganded structure revealed a large interdomain
conformational shift upon binding the DNA substrate
accompanied by local conformational changes in the
C-terminal domain zinc finger and N-terminal domain
void-filling loop necessary to position the enzyme on the
DNA. The detailed biochemical analysis of NEIL2 with an
array of oxidized base lesions indicates a significant
preference for its lyase activity likely to be paramount
when interpreting the biological consequences of
variants.
