Evidence map›Paper›PMID 29155430›Full record

ArticleNature chemical biology2018

Engineering peptide ligase specificity by proteomic identification of ligation sites.

Amy M Weeks, James A Wells

Abstract read
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Caspase-mediated cleavage events hidden by secondary proteolysis during apoptosis.Protein science : a publication of the Protein Society · 2026
    Article
  3. Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026
    Review
  4. Phosphoproteome-derived peptide libraries for deep specificity profiling of phosphatases and phospholyases.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Article
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  12. Review
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  14. Article
  15. Article
  16. Article
  17. An atlas of caspase cleavage events in differentiating muscle cells.Protein science : a publication of the Protein Society · 2024
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Amy M WeeksDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · US

Funding

Global Analysis of Proteolysis in ApoptosisR01GM081051 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2007 to 2015
$2.8M
Affinity-directed tagging of protein binding partners in signalingR01CA191018 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA191018NIGMS NIH HHS R01 GM081051
6 · The paper itself

Abstract

Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strategy to characterize the ligation efficiency for >25,000 enzyme-substrate pairs in the context of the engineered peptide ligase subtiligase and identified a family of 72 mutant subtiligases with activity toward N-terminal sequences that were previously recalcitrant to modification. We applied these mutants individually for site-specific bioconjugation of purified proteins, including antibodies, and in algorithmically selected combinations for sequencing of the cellular N terminome with reduced sequence bias. We also developed a web application to enable algorithmic selection of the most efficient subtiligase variant(s) for bioconjugation to user-defined sequences. Our methods provide a new toolbox of enzymes for site-specific protein modification and a general approach for rapidly defining and engineering peptide ligase specificity.

Indexed as

Peptide LibraryBinding SitesChromatography, LiquidHumansJurkat CellsKineticsLigandsModels, MolecularPeptide SynthasesPlasmidsProtein EngineeringProteomicsSubstrate SpecificitySubtilisinsTandem Mass SpectrometryLigandsPeptide LibraryPeptide SynthasessubtiligaseSubtilisins

Identifiers

PMID29155430
PMCPMC5726896
OpenAlexW2770432214

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.