Evidence mapPaperPMID 30520988Full record

ArticleNucleic acids research2019

Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site.

Sergey V Melnikov, Nelli F Khabibullina, Elisabeth Mairhofer, Oscar Vargas-Rodriguez, Noah M Reynolds, Ronald Micura, Dieter Söll, Yury S Polikanov

Abstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
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

28 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Co-Translational Incorporation ofJournal of the American Chemical Society · 2026
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  6. Mammalian Tolerance to Amino Acid Heterochirality.Chembiochem : a European journal of chemical biology · 2025
    Review
  7. Article
  8. Reprogramming the genetic code with flexizymes.Nature reviews. Chemistry · 2024
    Review
  9. Article
  10. Review
  11. Article
  12. Tuning tRNAs for improved translation.Frontiers in genetics · 2024
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Sergey V MelnikovDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Nelli F KhabibullinaDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Elisabeth MairhoferInstitute of Organic Chemistry at Leopold Franzens University, A-6020 Innsbruck, Austria.
Oscar Vargas-RodriguezDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Noah M ReynoldsDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Ronald MicuraInstitute of Organic Chemistry at Leopold Franzens University, A-6020 Innsbruck, Austria.
Dieter SöllDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Yury S PolikanovDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.

Funding

Austrian Science Fund FWF P 27947NCRR NIH HHS S10 RR029205NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R35 GM122560NIH HHS S10 OD021527
6 · The paper itself

Abstract

During protein synthesis, ribosomes discriminate chirality of amino acids and prevent incorporation of D-amino acids into nascent proteins by slowing down the rate of peptide bond formation. Despite this phenomenon being known for nearly forty years, no structures have ever been reported that would explain the poor reactivity of D-amino acids. Here we report a 3.7Å-resolution crystal structure of a bacterial ribosome in complex with a D-aminoacyl-tRNA analog bound to the A site. Although at this resolution we could not observe individual chemical groups, we could unambiguously define the positions of the D-amino acid side chain and the amino group based on chemical restraints. The structure reveals that similarly to L-amino acids, the D-amino acid binds the ribosome by inserting its side chain into the ribosomal A-site cleft. This binding mode does not allow optimal nucleophilic attack of the peptidyl-tRNA by the reactive α-amino group of a D-amino acid. Also, our structure suggests that the D-amino acid cannot participate in hydrogen-bonding with the P-site tRNA that is required for the efficient proton transfer during peptide bond formation. Overall, our work provides the first mechanistic insight into the ancient mechanism that helps living cells ensure the stereochemistry of protein synthesis.

Indexed as

Amino AcidsBinding SitesCatalytic DomainCrystallography, X-RayHydrogen BondingPeptidesProtein BiosynthesisRibosomesRNA, Transfer, Amino AcylAmino AcidsPeptidesRNA, Transfer, Amino AcyltRNA, peptidyl-

Identifiers

PMID30520988
PMCPMC6393236

What Socratic holds

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Registered trials

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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 Socratic graph.