3TAR

Crystal Structure of Bacillus DNA Polymerase I Large Fragment Bound to Duplex DNA with Cytosine-Adenine Mismatch at (n-6) Position

Summary for 3TAR

• Entry DOI: 10.2210/pdb3tar/pdb
• Related: 3TAN 3TAP 3TAQ 3THV 3TI0
• Related PRD ID: PRD_900003
• Descriptor: DNA polymerase I, 5'-D(*GP*CP*GP*AP*TP*CP*AP*CP*GP*CP*AP*CP*GP*TP*C)-3', 5'-D(*GP*AP*CP*GP*TP*AP*CP*GP*TP*GP*AP*TP*CP*GP*CP*A)-3', ... (7 entities in total)
• Functional Keywords: dna polymerase i, protein-dna complex, transferase-dna complex, transferase/dna
• Biological source: Geobacillus
• Total number of polymer chains: 3
• Total formula weight: 77993.55

Authors

Wang, W.,Beese, L.S. (deposition date: 2011-08-04, release date: 2011-10-19, Last modification date: 2023-09-13)

Primary citation

Wang, W.,Hellinga, H.W.,Beese, L.S.
Structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis.
Proc.Natl.Acad.Sci.USA, 108:17644-17648, 2011

PubMed Abstract: Even though high-fidelity polymerases copy DNA with remarkable accuracy, some base-pair mismatches are incorporated at low frequency, leading to spontaneous mutagenesis. Using high-resolution X-ray crystallographic analysis of a DNA polymerase that catalyzes replication in crystals, we observe that a C • A mismatch can mimic the shape of cognate base pairs at the site of incorporation. This shape mimicry enables the mismatch to evade the error detection mechanisms of the polymerase, which would normally either prevent mismatch incorporation or promote its nucleolytic excision. Movement of a single proton on one of the mismatched bases alters the hydrogen-bonding pattern such that a base pair forms with an overall shape that is virtually indistinguishable from a canonical, Watson-Crick base pair in double-stranded DNA. These observations provide structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis, a long-standing concept that has been difficult to demonstrate directly.

PubMed: 22006298
DOI: 10.1073/pnas.1114496108

Experimental method

X-RAY DIFFRACTION (1.6 Å)