Summary information and primary citation
- PDB-id
-
1yfh;
DSSR-derived features in text and
JSON formats
- Class
- transferase-DNA
- Method
- X-ray (3.01 Å)
- Summary
- Wt human o6-alkylguanine-DNA alkyltransferase bound to
DNA containing an alkylated cytosine
- Reference
-
Duguid EM, Rice PA, He C (2005): "The
structure of the human AGT protein bound to DNA and its
implications for damage detection."
J.Mol.Biol., 350, 657-666. doi:
10.1016/j.jmb.2005.05.028.
- Abstract
- O6-Alklyguanine-DNA alkyltransferase (AGT) is an
important DNA repair protein that protects cells from
mutagenesis and toxicity arising from alkylating agents. We
present an X-ray crystal structure of the wild-type human
protein (hAGT) bound to double-stranded DNA with a
chemically modified cytosine base. The protein binds at two
different sites: one at the modified base, and the other
across a sticky-ended DNA junction. The protein molecule
that binds the modified cytosine base flips the base and
recognizes it in its active site. The one that binds ends
of neighboring DNA molecules partially flips an overhanging
thymine base. This base is not inserted into the
active-site pocket of the protein. These two different
hAGT/DNA interactions observed in the structure suggest
that hAGT may not detect DNA lesions by searching for the
adduct itself, but rather for weakened and/or distorted
base-pairs caused by base damage in the duplex DNA. We
propose that hAGT imposes a strain on the DNA duplex and
searches for DNA regions where the native structure is
destabilized. The structure provides implications for
pyrimidine recognition, improved inhibitor design, and a
possible protein/protein interaction patch on hAGT.
