English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Deoxynucleotide misincorporation efficiencies can span a wide 10 4 -fold range, from ∼10 -2 to ∼10 -6 , depending principally on polymerase (pol) identity and DNA sequence context. We have addressed DNA pol fidelity mechanisms from a transition-state (TS) perspective using our "tool-kit" of dATP- and dGTP-β,γ substrate analogues in which the pyrophosphate leaving group (p K a4 = 8.9) has been replaced by a series of bisphosphonates covering a broad acidity range spanning p K a4 values from 7.8 (CF 2 ) to 12.3 [C(CH 3 ) 2 ]. Here, we have used a linear free energy relationship (LFER) analysis, in the form of a Brønsted plot of log( k pol ) versus p K a4 , for Y-family error-prone pol η and X-family pols λ and β to determine the extent to which different electrostatic active site environments alter k pol values. The apparent chemical rate constant ( k pol ) is the rate-determining step for the three pols. The pols each exhibit a distinct catalytic signature that differs for formation of right (A·T) and wrong (G·T) incorporations observed as changes in slopes and displacements of the Brønsted lines, in relation to a reference LFER. Common to this signature among all three pols is a split linear pattern in which the analogues containing two halogens show k pol values that are systematically lower than would be predicted from their p K a4 values measured in aqueous solution. We discuss how metal ions and active site amino acids are responsible for causing "effective" p K a4 values that differ for dihalo and non-dihalo substrates as well as for individual R and S stereoisomers for CHF and CHCl.

A Transition-State Perspective on Y-Family DNA Polymerase η Fidelity in Comparison with X-Family DNA Polymerases λ and β