Evidence map›Paper›PMID 25961938›Full record

ArticleJournal of the American Chemical Society2015

Structural basis for a six nucleotide genetic alphabet.

Millie M Georgiadis, Isha Singh, Whitney F Kellett, Shuichi Hoshika, Steven A Benner, Nigel G J Richards

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Simulation- and AI-directed optimization of 4,6-substituted 1,3,5-triazin-2(1Computational and structural biotechnology journal · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Investigation of the stability of D5SIC-DNAM-incorporated DNA duplex inPhysical chemistry chemical physics : PCCP · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Crystal structures of 'ALternative Isoinformational ENgineered' DNA in B-form.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  17. Discovery, implications and initial use of semi-synthetic organisms with an expanded genetic alphabet/code.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Millie M Georgiadis
Isha Singh
Whitney F Kellett
Shuichi Hoshika
Steven A Benner
Nigel G J Richards

Funding

Biochemical Studies of Oxalate DecarboxylaseR01DK061666 · NIDDK · UNIVERSITY OF FLORIDA · PI RICHARDS, NIGEL GORDON · 2003 to 2013
$1.9M
Expanded DNA, In Vitro Selection, Aptamers, and CancerR01GM111386 · NIGMS · FOUNDATION FOR APPLIED MOLECULAR EVOLUTN · PI BENNER, STEVEN A · 2014 to 2016
$1.2M
NCI NIH HHS Y1-CO-1020NIDDK NIH HHS R01 DK061666NIDDK NIH HHS R01DK061666NIGMS NIH HHS R01 GM111386NIGMS NIH HHS R01GM111386NIGMS NIH HHS Y1-GM-1104
6 · The paper itself

Abstract

Expanded genetic systems are most likely to work with natural enzymes if the added nucleotides pair with geometries that are similar to those displayed by standard duplex DNA. Here, we present crystal structures of 16-mer duplexes showing this to be the case with two nonstandard nucleobases (Z, 6-amino-5-nitro-2(1H)-pyridone and P, 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one) that were designed to form a Z:P pair with a standard "edge on" Watson-Crick geometry, but joined by rearranged hydrogen bond donor and acceptor groups. One duplex, with four Z:P pairs, was crystallized with a reverse transcriptase host and adopts primarily a B-form. Another contained six consecutive Z:P pairs; it crystallized without a host in an A-form. In both structures, Z:P pairs fit canonical nucleobase hydrogen-bonding parameters and known DNA helical forms. Unique features include stacking of the nitro group on Z with the adjacent nucleobase ring in the A-form duplex. In both B- and A-duplexes, major groove widths for the Z:P pairs are approximately 1 Å wider than those of comparable G:C pairs, perhaps to accommodate the large nitro group on Z. Otherwise, ZP-rich DNA had many of the same properties as CG-rich DNA, a conclusion supported by circular dichroism studies in solution. The ability of standard duplexes to accommodate multiple and consecutive Z:P pairs is consistent with the ability of natural polymerases to biosynthesize those pairs. This, in turn, implies that the GACTZP synthetic genetic system can explore the entire expanded sequence space that additional nucleotides create, a major step forward in this area of synthetic biology.

Indexed as

DNAGenetic CodeHydrogen BondingModels, MolecularNucleotidesSynthetic BiologyDNANucleotides

Identifiers

PMID25961938
PMCPMC4633024

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.