Evidence map›Paper›PMID 29051530›Full record

ArticleNature communications2017

Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates.

Clarissa M Czekster, Hannes Ludewig, Stephen A McMahon, James H Naismith

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Review
  3. Use of a head-to-tail peptide cyclase to prepare hybrid RiPPs.Chemical communications (Cambridge, England) · 2024
    Article
  4. Review
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  6. Article
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  11. Chirality-matched catalyst-controlled macrocyclization reactions.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
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

4 authors at 2 institutions in 2 countries.

Clarissa M CzeksterBiomedical Sciences Research Complex, The University of St Andrews, North Haugh, St Andrews, K16 9ST, UK.ORCID http://orcid.org/0000-0002-7163-4057
Hannes LudewigBiomedical Sciences Research Complex, The University of St Andrews, North Haugh, St Andrews, K16 9ST, UK.ORCID http://orcid.org/0000-0003-1130-1442
Stephen A McMahonBiomedical Sciences Research Complex, The University of St Andrews, North Haugh, St Andrews, K16 9ST, UK.
James H NaismithBiomedical Sciences Research Complex, The University of St Andrews, North Haugh, St Andrews, K16 9ST, UK. naismith@strubi.ox.ac.uk.
University of St Andrews · GBCentre for Human Genetics · GB

Funding

European Research Council 339367
6 · The paper itself

Abstract

Peptide macrocycles are promising therapeutic molecules because they are protease resistant, structurally rigid, membrane permeable, and capable of modulating protein-protein interactions. Here, we report the characterization of the dual function macrocyclase-peptidase enzyme involved in the biosynthesis of the highly toxic amanitin toxin family of macrocycles. The enzyme first removes 10 residues from the N-terminus of a 35-residue substrate. Conformational trapping of the 25 amino-acid peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization. The enzyme rebinds the 25 amino-acid peptide in a different conformation and catalyzes macrocyclization of the N-terminal eight residues. Structures of the enzyme bound to both substrates and biophysical analysis characterize the different binding modes rationalizing the mechanism. Using these insights simpler substrates with only five C-terminal residues were designed, allowing the enzyme to be more effectively exploited in biotechnology.

Indexed as

AmanitinsBasidiomycotaCyclizationKineticsModels, MolecularMutationPeptide HydrolasesAmanitinsPeptide Hydrolases

Identifiers

PMID29051530
PMCPMC5648786
OpenAlexW2761775375

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.