Evidence map›Paper›PMID 26680698›Full record

ArticleNature communications2015

Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase.

Karen S Harris, Thomas Durek, Quentin Kaas, Aaron G Poth, Edward K Gilding, Brendon F Conlan, Ivana Saska, Norelle L Daly, Nicole L van der Weerden, David J Craik and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
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

117 citing papers in PubMed, 256 citations in OpenAlex.

  1. Review
  2. Article
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  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Metabolite Mediated Protein Macrocyclization.Synlett : accounts and rapid communications in synthetic organic chemistry · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Structural Basis of High-Precision Protein Ligation and Its Application.Journal of the American Chemical Society · 2025
    Article
  19. Highly Efficient Transpeptidase-Catalyzed Isopeptide Ligation.Journal of the American Chemical Society · 2025
    Article
  20. Development of protein chemical synthesis using peptide thioester synthetic blocks.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025
    Review

57 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 1 country.

Karen S HarrisDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Thomas DurekDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Quentin KaasDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Aaron G PothDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Edward K GildingDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Brendon F ConlanDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Ivana SaskaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Norelle L DalyDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Nicole L van der WeerdenDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
David J CraikDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Marilyn A AndersonDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
University of Queensland · AULa Trobe University · AUAustralian Institute of Tropical Health and Medicine · AUAustralian National University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclotides are diverse plant backbone cyclized peptides that have attracted interest as pharmaceutical scaffolds, but fundamentals of their biosynthetic origin remain elusive. Backbone cyclization is a key enzyme-mediated step of cyclotide biosynthesis and confers a measure of stability on the resultant cyclotide. Furthermore, cyclization would be desirable for engineered peptides. Here we report the identification of four asparaginyl endopeptidases (AEPs), proteases implicated in cyclization, from the cyclotide-producing plant Oldenlandia affinis. We recombinantly express OaAEP1b and find it functions preferably as a cyclase by coupling C-terminal cleavage of propeptide substrates with backbone cyclization. Interestingly, OaAEP1b cannot cleave at the N-terminal site of O. affinis cyclotide precursors, implicating additional proteases in cyclotide biosynthesis. Finally, we demonstrate the broad utility of this enzyme by cyclization of peptides unrelated to cyclotides. We propose that recombinant OaAEP1b is a powerful tool for use in peptide engineering applications where increased stability of peptide products is desired.

Indexed as

Asparaginyl EndopeptidaseCyclizationCysteine EndopeptidasesGene Expression ProfilingMagnetic Resonance SpectroscopyMass SpectrometryOldenlandiaPeptidesPlant ProteinsRecombinant ProteinsRNA, MessengerAsparaginyl EndopeptidaseCysteine EndopeptidasesPeptidesPlant ProteinsRecombinant ProteinsRNA, Messenger

Identifiers

PMID26680698
PMCPMC4703859
OpenAlexW2267190811

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.