5WN4

APE1 exonuclease substrate complex with a C/T mismatch

Summary for 5WN4

• Entry DOI: 10.2210/pdb5wn4/pdb
• Descriptor: DNA (5'-D(P*TP*CP*GP*AP*CP*GP*GP*AP*TP*CP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*(DV3))-3'), DNA (5'-D(*GP*GP*AP*TP*CP*CP*GP*TP*CP*GP*AP*TP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), ... (9 entities in total)
• Functional Keywords: hydrolase, lyase-dna complex, lyase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 75416.99

Authors

Freudenthal, B.D.,Whitaker, A.M. (deposition date: 2017-07-31, release date: 2018-02-28, Last modification date: 2023-10-04)

Primary citation

Whitaker, A.M.,Flynn, T.S.,Freudenthal, B.D.
Molecular snapshots of APE1 proofreading mismatches and removing DNA damage.
Nat Commun, 9:399-399, 2018

PubMed 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.

PubMed: 29374164
DOI: 10.1038/s41467-017-02175-y

Experimental method

X-RAY DIFFRACTION (2.1 Å)