Summary information and primary citation
- PDB-id
-
5vi0;
DSSR-derived features in text and
JSON formats
- Class
- hydrolase-DNA
- Method
- X-ray (2.396 Å)
- Summary
- Pseudomonas fluorescens alkylpurine DNA glycosylase
alkc bound to DNA containing an abasic site analog
- Reference
-
Shi R, Mullins EA, Shen XX, Lay KT, Yuen PK, David SS,
Rokas A, Eichman BF (2018): "Selective
base excision repair of DNA damage by the
non-base-flipping DNA glycosylase AlkC." EMBO
J., 37, 63-74. doi: 10.15252/embj.201797833.
- Abstract
- DNA glycosylases preserve genome integrity and define
the specificity of the base excision repair pathway for
discreet, detrimental modifications, and thus, the
mechanisms by which glycosylases locate DNA damage are of
particular interest. Bacterial AlkC and AlkD are specific
for cationic alkylated nucleobases and have a distinctive
HEAT-like repeat (HLR) fold. AlkD uses a unique
non-base-flipping mechanism that enables excision of bulky
lesions more commonly associated with nucleotide excision
repair. In contrast, AlkC has a much narrower specificity
for small lesions, principally N3-methyladenine (3mA).
Here, we describe how AlkC selects for and excises 3mA
using a non-base-flipping strategy distinct from that of
AlkD. A crystal structure resembling a catalytic
intermediate complex shows how AlkC uses unique HLR and
immunoglobulin-like domains to induce a sharp kink in the
DNA, exposing the damaged nucleobase to active site
residues that project into the DNA This active site
can accommodate and excise N3-methylcytosine (3mC) and
N1-methyladenine (1mA), which are also repaired by
AlkB-catalyzed oxidative demethylation, providing a
potential alternative mechanism for repair of these lesions
in bacteria.
