Evidence map›Paper›PMID 28943336›Full record

ArticleStructure (London, England : 1993)2017

The Origins of Specificity in the Microcin-Processing Protease TldD/E.

Dmitry Ghilarov, Marina Serebryakova, Clare E M Stevenson, Stephen J Hearnshaw, Dmitry S Volkov, Anthony Maxwell, David M Lawson, Konstantin Severinov

Open access · hybridAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Biosynthesis of the Biphenomycin Family of Potent Antibiotics.Angewandte Chemie (International ed. in English) · 2025
    Article
  3. Article
  4. Article
  5. Biosynthesis of Macrocyclic Peptides by Formation and Crosslinking ofbioRxiv : the preprint server for biology · 2025
    Article
  6. Enterolyin S, a Polythiazole-containing Hemolytic Peptide from Enterococcus caccae.Chembiochem : a European journal of chemical biology · 2024
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. A two-component protease inThe Journal of biological chemistry · 2019
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Frontiers in cellular and infection microbiology · 2018
    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 5 institutions in 3 countries.

Dmitry GhilarovCentre for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia; Institute of Gene Biology of the Russian Academy of Sciences, 119334 Moscow, Russia; Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: dmitry.gilyarov@uj.edu.pl.
Marina SerebryakovaInstitute of Gene Biology of the Russian Academy of Sciences, 119334 Moscow, Russia; Lomonosov Moscow State University, Department of Chemistry, A.N. Belozersky Institute of Physico-Chemical Biology, 119992 Moscow, Russia.
Clare E M StevensonDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Stephen J HearnshawDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Dmitry S VolkovLomonosov Moscow State University, Department of Chemistry, Analytical Chemistry Division, 119991 Moscow, Russia.
Anthony MaxwellDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
David M LawsonDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Konstantin SeverinovCentre for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia; Bionano Institute, Peter the Great Saint Petersburg State Polytechnical University, Saint Petersburg 195251, Russia; Waksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: severik@waksman.rutgers.edu.
Institute of Gene Biology · RUJohn Innes Centre · GBNorwich Research Park · GBLomonosov Moscow State University · RUSkolkovo Institute of Science and Technology · RU

Funding

Biotechnology and Biological Sciences Research Council BB/J004561/1Biotechnology and Biological Sciences Research Council BB/J016853/1Biotechnology and Biological Sciences Research Council BBS/E/J/00000201
6 · The paper itself

Abstract

TldD and TldE proteins are involved in the biosynthesis of microcin B17 (MccB17), an Escherichia coli thiazole/oxazole-modified peptide toxin targeting DNA gyrase. Using a combination of biochemical and crystallographic methods we show that E. coli TldD and TldE interact to form a heterodimeric metalloprotease. TldD/E cleaves the N-terminal leader sequence from the modified MccB17 precursor peptide, to yield mature antibiotic, while it has no effect on the unmodified peptide. Both proteins are essential for the activity; however, only the TldD subunit forms a novel metal-containing active site within the hollow core of the heterodimer. Peptide substrates are bound in a sequence-independent manner through β sheet interactions with TldD and are likely cleaved via a thermolysin-type mechanism. We suggest that TldD/E acts as a "molecular pencil sharpener": unfolded polypeptides are fed through a narrow channel into the active site and processively truncated through the cleavage of short peptides from the N-terminal end.

Indexed as

BacteriocinsCatalytic DomainCrystallography, X-RayEscherichia coliEscherichia coli ProteinsModels, MolecularPeptide HydrolasesPeptidesProtein ConformationSubstrate SpecificityBacteriocinsEscherichia coli ProteinsmicrocinPeptide HydrolasesPeptidesTldD protein, E coliTldE protein, E coliCcdABDNA gyrasemetalloproteasemicrocin B17peptidaseribosomally synthesized modified peptidesRiPPtoxin-antitoxinX-ray crystallography

Identifiers

PMID28943336
PMCPMC5810440
OpenAlexW2757083063

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.