5VU5

TNA polymerase, apo

Summary for 5VU5

• Entry DOI: 10.2210/pdb5vu5/pdb
• Related: 5VU6 5VU7 5VU8 5VU9
• Descriptor: DNA polymerase (1 entity in total)
• Functional Keywords: protein-nucleic acid complex, transferase
• Biological source: Thermococcus kodakarensis
• Total number of polymer chains: 1
• Total formula weight: 90130.62

Authors

Chim, N.,Chaput, J.C. (deposition date: 2017-05-18, release date: 2017-12-06, Last modification date: 2024-11-06)

Primary citation

Chim, N.,Shi, C.,Sau, S.P.,Nikoomanzar, A.,Chaput, J.C.
Structural basis for TNA synthesis by an engineered TNA polymerase.
Nat Commun, 8:1810-1810, 2017

PubMed Abstract: Darwinian evolution experiments carried out on xeno-nucleic acid (XNA) polymers require engineered polymerases that can faithfully and efficiently copy genetic information back and forth between DNA and XNA. However, current XNA polymerases function with inferior activity relative to their natural counterparts. Here, we report five X-ray crystal structures that illustrate the pathway by which α-(L)-threofuranosyl nucleic acid (TNA) triphosphates are selected and extended in a template-dependent manner using a laboratory-evolved polymerase known as Kod-RI. Structural comparison of the apo, binary, open and closed ternary, and translocated product detail an ensemble of interactions and conformational changes required to promote TNA synthesis. Close inspection of the active site in the closed ternary structure reveals a sub-optimal binding geometry that explains the slow rate of catalysis. This key piece of information, which is missing for all naturally occurring archaeal DNA polymerases, provides a framework for engineering new TNA polymerase variants.

PubMed: 29180809
DOI: 10.1038/s41467-017-02014-0

Experimental method

X-RAY DIFFRACTION (2.8 Å)