Summary information and primary citation

PDB-id
5wn5; SNAP-derived features in text and JSON formats; DNAproDB
Class
hydrolase, lyase-DNA
Method
X-ray (2.2 Å)
Summary
Ape1 exonuclease substrate complex with a c-t mismatch and mn2+
Reference
Whitaker AM, Flynn TS, Freudenthal BD (2018): "Molecular snapshots of APE1 proofreading mismatches and removing DNA damage." Nat Commun, 9, 399. doi: 10.1038/s41467-017-02175-y.
Abstract
Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair enzyme which uses a single active site to process DNA damage via two distinct activities: (1) AP-endonuclease and (2) 3' to 5' exonuclease. The AP-endonuclease activity cleaves at AP-sites, while the exonuclease activity excises bulkier 3' mismatches and DNA damage to generate clean DNA ends suitable for downstream repair. Molecular details of the exonuclease reaction and how one active site can accommodate various toxic DNA repair intermediates remains elusive despite being biologically important. Here, we report multiple high-resolution APE1-DNA structural snapshots revealing how APE1 removes 3' mismatches and DNA damage by placing the 3' group within the intra-helical DNA cavity via a non-base flipping mechanism. This process is facilitated by a DNA nick, instability of a mismatched/damaged base, and bending of the DNA. These results illustrate how APE1 cleanses DNA dirty-ends to generate suitable substrates for downstream repair enzymes.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js