SNAP output for PDB entry 5nkl [SNAP web server]

PDB-id

5nkl; SNAP-derived features in text and JSON formats; DNAproDB

Class

transferase

Method

X-ray (1.7 Å)

Summary

Crystal structure of the large fragment of DNA polymerase i from thermus aquaticus in a closed ternary complex with the artificial base pair dds-dpxtp

Reference

Betz K, Kimoto M, Diederichs K, Hirao I, Marx A (2017): "Structural Basis for Expansion of the Genetic Alphabet with an Artificial Nucleobase Pair." Angew. Chem. Int. Ed. Engl., 56, 12000-12003. doi: 10.1002/anie.201704190.

Abstract

Hydrophobic artificial nucleobase pairs without the ability to pair via hydrogen bonds are promising candidates to expand the genetic alphabet. The most successful nucleobase surrogates show little similarity with each other and with their natural counterparts. Thus, it is puzzling how the unnatural molecules are processed by DNA polymerases that have evolved to efficiently work with the natural building blocks. Here we report structural insights into the insertion of one of the most promising hydrophobic unnatural base pairs; the dDs-dPx pair into a DNA strand by a DNA polymerase. We solved a crystal structure of KlenTaq DNA polymerase with a modified template/primer duplex bound to the unnatural triphosphate. The ternary complex shows that the artificial pair adopts a planar structure just like a natural nucleobase pair and identifies features that might hint to the mechanisms accounting for the lower incorporation efficiency when processing the unnatural substrates.