Evidence map›Paper›PMID 24421400›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014

Structure and protective efficacy of the Staphylococcus aureus autocleaving protease EpiP.

Misty L Kuhn, Prachi Prachi, George Minasov, Ludmilla Shuvalova, Jiapeng Ruan, Ievgeniia Dubrovska, James Winsor, Monica Giraldi, Massimiliano Biagini, Sabrina Liberatori and 4 more

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. CylA is a sequence-specific protease involved in toxin biosynthesis.Journal of industrial microbiology & biotechnology · 2019
    Article
  7. Comparative Secretome Analyses of Human and ZoonoticMolecular & cellular proteomics : MCP · 2018
    Article
  8. Article
  9. Frontiers in cellular and infection microbiology · 2017
    Review
  10. Article
  11. Article
  12. Structure and mechanism of lanthipeptide biosynthetic enzymes.Current opinion in structural biology · 2014
    Review
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

14 authors.

Misty L Kuhn2G.G., Novartis Vaccines, via Fiorentina 1, 53100, Siena, Italy. guido.grandi@novartis.com.
Prachi Prachi
George Minasov
Ludmilla Shuvalova
Jiapeng Ruan
Ievgeniia Dubrovska
James Winsor
Monica Giraldi
Massimiliano Biagini
Sabrina Liberatori
Silvana Savino
Fabio Bagnoli
Wayne F Anderson
Guido Grandi

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
NCI NIH HHS P30 CA060553NIAID NIH HHS HHSN272200700058CNIAID NIH HHS HHSN272201200026C
6 · The paper itself

Abstract

Despite the global medical needs associated with Staphylococcus aureus infections, no licensed vaccines are currently available. We identified and characterized a protein annotated as an epidermin leader peptide processing serine protease (EpiP), as a novel S. aureus vaccine candidate. In addition, we determined the structure of the recombinant protein (rEpiP) by X-ray crystallography. The crystal structure revealed that rEpiP was cleaved somewhere between residues 95 and 100, and we found that the cleavage occurs through an autocatalytic intramolecular mechanism. The protein expressed by S. aureus cells also appeared to undergo a similar processing event. To determine whether the protein acts as a serine protease, we mutated the hypothesized catalytic serine 393 residue to alanine, generating rEpiP-S393A. The crystal structure of this mutant protein showed that the polypeptide chain was not cleaved and was not interacting stably with the active site. Indeed, rEpiP-S393A was shown to be impaired in its protease activity. Mice vaccinated with rEpiP were protected from S. aureus infection (34% survival, P=0.0054). Moreover, the protective efficacy generated by rEpiP and rEpiP-S393A was comparable, implying that the noncleaving mutant could be used for vaccination purposes.

Indexed as

AnimalsBacterial ProteinsBacterial VaccinesBiocatalysisBlotting, WesternCatalytic DomainCrystallography, X-RayMiceModels, MolecularMutationProtein ConformationRecombinant ProteinsSerine EndopeptidasesStaphylococcal InfectionsStaphylococcus aureusStatic ElectricityBacterial ProteinsBacterial VaccinesEpiP serine proteaseRecombinant ProteinsSerine Endopeptidasesabscessepidermin leader peptide processing serine proteaseimmunogenicitylantibioticpathogenesisvaccine

Identifiers

PMID24421400
PMCPMC3963019

What OpenQuestion holds

Textmetadata
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.