4PGQ

Structure of human DNA polymerase beta complexed with G in the template base paired with incoming non-hydrolyzable TTP

Summary for 4PGQ

• Entry DOI: 10.2210/pdb4pgq/pdb
• Descriptor: DNA polymerase beta, DNA (5'-D(*CP*CP*GP*AP*CP*GP*TP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*A)-3'), ... (8 entities in total)
• Functional Keywords: dna polymerase, nucleotidyl synthesis, transferase, lyase-dna complex, lyase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 47577.75

Authors

Koag, M.C.,Lee, S. (deposition date: 2014-05-02, release date: 2014-10-01, Last modification date: 2023-12-27)

Primary citation

Koag, M.C.,Nam, K.,Lee, S.
The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase beta.
Nucleic Acids Res., 42:11233-11245, 2015

PubMed Abstract: To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg(2+)-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an 'intermediate' protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn(2+)-bound 'pre-chemistry-state' structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson-Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson-Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson-Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ.

PubMed: 25200079
DOI: 10.1093/nar/gku789

Experimental method

X-RAY DIFFRACTION (2.3 Å)