AI Article Synopsis
- Replicative DNA polymerases are enzymes that carefully control the shape and orientation of DNA during synthesis, but the bacterial polymerase from Geobacillus stearothermophilus (Bst) can also reverse transcribe RNA and other synthetic nucleotides into DNA.
- The study presents crystal structures of Bst DNA polymerase synthesizing DNA from unique templates made of 2'-deoxy-2'-fluoro-β-d-arabino nucleic acid (FANA) and α-l-threofuranosyl nucleic acid (TNA).
- It highlights the enzyme's structural flexibility as a key factor for its ability to synthesize DNA using these diverse chemical templates, which could lead to the development of enhanced enzyme variants.
Article Abstract
Replicative DNA polymerases are highly efficient enzymes that maintain stringent geometric control over shape and orientation of the template and incoming nucleoside triphosphate. In a surprising twist to this paradigm, a naturally occurring bacterial DNA polymerase I member isolated from Geobacillus stearothermophilus (Bst) exhibits an innate ability to reverse transcribe RNA and other synthetic congeners (XNAs) into DNA. This observation raises the interesting question of how a replicative DNA polymerase is able to recognize templates of diverse chemical composition. Here, we present crystal structures of natural Bst DNA polymerase that capture the post-translocated product of DNA synthesis on templates composed entirely of 2'-deoxy-2'-fluoro-β-d-arabino nucleic acid (FANA) and α-l-threofuranosyl nucleic acid (TNA). Analysis of the enzyme active site reveals the importance of structural plasticity as a possible mechanism for XNA-dependent DNA synthesis and provides insights into the construction of variants with improved activity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649750 | PMC |
| http://dx.doi.org/10.1093/nar/gkz513 | DOI Listing |
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