ArticleBiochemistry2012
Probing minor groove hydrogen bonding interactions between RB69 DNA polymerase and DNA.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Structure of New Binary and Ternary DNA Polymerase Complexes From Bacteriophage RB69.Frontiers in molecular biosciences · 2021Article
- Mutagenesis mechanism of the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine.Nucleic acids research · 2020Article
- Insights into the effect of minor groove interactions and metal cofactors on mutagenic replication by human DNA polymerase β.The Biochemical journal · 2018Article
- NAngewandte Chemie (International ed. in English) · 2017Article
- RB69 DNA polymerase structure, kinetics, and fidelity.Biochemistry · 2014Review
- Mispairs with Watson-Crick base-pair geometry observed in ternary complexes of an RB69 DNA polymerase variant.Protein science : a publication of the Protein Society · 2014Article
- Structural basis for processive DNA synthesis by yeast DNA polymerase ɛ.Nature structural & molecular biology · 2014Article
- Alteration in the cavity size adjacent to the active site of RB69 DNA polymerase changes its conformational dynamics.Nucleic acids research · 2013Article
- DNA mismatch synthesis complexes provide insights into base selectivity of a B family DNA polymerase.Journal of the American Chemical Society · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Minor groove hydrogen bonding (HB) interactions between DNA polymerases (pols) and N3 of purines or O2 of pyrimidines have been proposed to be essential for DNA synthesis from results obtained using various nucleoside analogues lacking the N3 or O2 contacts that interfered with primer extension. Because there has been no direct structural evidence to support this proposal, we decided to evaluate the contribution of minor groove HB interactions with family B pols. We have used RB69 DNA pol and 3-deaza-2'-deoxyadenosine (3DA), an analogue of 2-deoxyadenosine, which has the same HB pattern opposite T but with N3 replaced with a carbon atom. We then determined pre-steady-state kinetic parameters for the insertion of dAMP opposite dT using primer/templates (P/T)-containing 3DA. We also determined three structures of ternary complexes with 3DA at various positions in the duplex DNA substrate. We found that the incorporation efficiency of dAMP opposite dT decreased 10(2)-10(3)-fold even when only one minor groove HB interaction was missing. Our structures show that the HB pattern and base pair geometry of 3DA/dT is exactly the same as those of dA/dT, which makes 3DA an optimal analogue for probing minor groove HB interactions between a DNA polymerase and a nucleobase. In addition, our structures provide a rationale for the observed 10(2)-10(3)-fold decrease in the rate of nucleotide incorporation. The minor groove HB interactions between position n - 2 of the primer strand and RB69pol fix the rotomer conformations of the K706 and D621 side chains, as well as the position of metal ion A and its coordinating ligands, so that they are in the optinal orientation for DNA synthesis.
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