Evidence map›Paper›PMID 36734655›Full record

ArticleBiochemistry2023

Peptidase Activation by a Leader Peptide-Bound RiPP Recognition Element.

Ashley M Kretsch, Mayuresh G Gadgil, Adam J DiCaprio, Susanna E Barrett, Bryce L Kille, Yuanyuan Si, Lingyang Zhu, Douglas A Mitchell

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

21 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Tangled Tail of Mechanically Interlocked Peptides.Journal of the American Chemical Society · 2026
    Review
  3. Article
  4. Article
  5. De novo Folding Mechanisms of Lasso Peptides.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Peptidic Tryptophan Halogenation by a Promiscuous Flavin-Dependent Enzyme.Angewandte Chemie (International ed. in English) · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

8 authors at 2 institutions in 1 country.

Ashley M KretschCarl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois61801, United States.
Mayuresh G GadgilCarl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois61801, United States.
Adam J DiCaprioCarl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois61801, United States.
Susanna E BarrettCarl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois61801, United States.
Bryce L KilleDepartment of Computer Science, Rice University, Houston, Texas77005, United States.
Yuanyuan SiCarl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois61801, United States.
Lingyang ZhuSchool of Chemical Sciences, NMR Laboratory, University of Illinois, Urbana, Illinois61801, United States.ORCID 0000-0002-6657-271X
Douglas A MitchellCarl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois61801, United States.ORCID 0000-0002-9564-0953
University of Illinois Urbana-Champaign · USRice University · US

Funding

TRAINING PROGRAM IN COMPUTATIONAL BIOLOGY AND MEDICINET15LM007093 · NLM · RICE UNIVERSITY · PI Lydia E. Kavraki · 1992 to 2026
$20.8M
Training Program in Chemistry-Interface with BiologyT32GM070421 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI HERGENROTHER, PAUL · 2005 to 2019
$5.4M
Training Program at the Chemistry Biology InterfaceT32GM136629 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Paul Hergenrother · 2020 to 2026
$4.5M
Genomics-Accelerated Natural Product DiscoveryR01GM123998 · NIGMS · VANDERBILT UNIVERSITY · PI MITCHELL, DOUGLAS ALAN · 2017 to 2024
$2.6M
Uniquely constrained peptides for modulating TNF receptor activityF32GM145122 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KRETSCH, ASHLEY M. · 2022 to 2022
$68k
NIGMS NIH HHS F32 GM145122NIGMS NIH HHS R01 GM123998NIGMS NIH HHS T32 GM070421NIGMS NIH HHS T32 GM136629NLM NIH HHS T15 LM007093
6 · The paper itself

Abstract

The RiPP precursor recognition element (RRE) is a conserved domain found in many prokaryotic ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic gene clusters (BGCs). RREs bind with high specificity and affinity to a recognition sequence within the N-terminal leader region of RiPP precursor peptides. Lasso peptide biosynthesis involves an RRE-dependent leader peptidase, which is discretely encoded or fused to the RRE as a di-domain protein. Here we leveraged thousands of predicted BGCs to define the RRE:leader peptidase interaction through evolutionary covariance analysis. Each interacting domain contributes a three-stranded β-sheet to form a hydrophobic β-sandwich-like interface. The bioinformatics-guided predictions were experimentally confirmed using proteins from discrete and fused lasso peptide BGC architectures. Support for the domain-domain interface derived from chemical shift perturbation, paramagnetic relaxation enhancement experiments, and rapid variant activity screening using cell-free biosynthesis. Further validation of selected variants was performed with purified proteins. We developed a

Indexed as

Peptide HydrolasesProtein Sorting SignalsBacterial ProteinsPeptidesProtein Processing, Post-TranslationalBacterial ProteinsPeptide HydrolasesPeptidesProtein Sorting Signals

Identifiers

PMID36734655
PMCPMC10126823
OpenAlexW4319063042

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.