Summary information and primary citation
- PDB-id
-
7cd5;
SNAP-derived features in text and
JSON formats
- Class
- hydrolase-DNA
- Method
- X-ray (2.7 Å)
- Summary
- Mape1-blunt-ended dsDNA product complex
- Reference
-
Liu TC, Lin CT, Chang KC, Guo KW, Wang S, Chu JW, Hsiao
YY (2021): "APE1
distinguishes DNA substrates in exonucleolytic cleavage
by induced space-filling." Nat Commun,
12, 601. doi: 10.1038/s41467-020-20853-2.
- Abstract
- The exonuclease activity of Apurinic/apyrimidinic
endonuclease 1 (APE1) is responsible for processing
matched/mismatched terminus in various DNA repair pathways
and for removing nucleoside analogs associated with drug
resistance. To fill in the gap of structural basis for
exonucleolytic cleavage, we determine the APE1-dsDNA
complex structures displaying end-binding. As an
exonuclease, APE1 does not show base preference but can
distinguish dsDNAs with different structural features.
Integration with assaying enzyme activity and binding
affinity for a variety of substrates reveals for the first
time that both endonucleolytic and exonucleolytic cleavage
can be understood by an induced space-filling model.
Binding dsDNA induces RM (Arg176 and Met269) bridge that
defines a long and narrow product pocket for exquisite
machinery of substrate selection. Our study paves the way
to comprehend end-processing of dsDNA in the cell and the
drug resistance relating to APE1.
