 |
PDBsum entry 7cd5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/DNA
|
PDB id
|
|
|
|
7cd5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Ape1 distinguishes DNA substrates in exonucleolytic cleavage by induced space-Filling.
|
|
|
Authors
|
|
T.C.Liu,
C.T.Lin,
K.C.Chang,
K.W.Guo,
S.Wang,
J.W.Chu,
Y.Y.Hsiao.
|
|
|
Ref.
|
|
Nat Commun, 2021,
12,
601.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
