Evidence map›Paper›PMID 18769623›Full record

ArticlePloS one2008

Role of N-terminal amino acids in the potency of anthrax lethal factor.

Pradeep K Gupta, Mahtab Moayeri, Devorah Crown, Rasem J Fattah, Stephen H Leppla

Abstract read
In one paragraph

Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed.

  1. Article
  2. Article
  3. ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  4. Article
  5. Review
  6. Article
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  11. Solid tumor therapy by selectively targeting stromal endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  12. Review
  13. Article
  14. Article
  15. Review
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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

5 authors.

Pradeep K GuptaLaboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Mahtab Moayeri
Devorah Crown
Rasem J Fattah
Stephen H Leppla

Funding

Structure and Function of Virulence Factors of Bacillus anthracisZIAAI001031 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LEPPLA, STEPHEN · 2009 to 2018
$6.2M
Structure and Function of Virulence Factors of Bacillus anthracis Z01AI001031 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LEPPLA, STEPHEN · 2008 to 2008
$899k
Intramural NIH HHS
6 · The paper itself

Abstract

Anthrax lethal factor (LF) is a Zn(+2)-dependent metalloprotease that cleaves several MAPK kinases and is responsible for the lethality of anthrax lethal toxin (LT). We observed that a recombinant LF (LF-HMA) which differs from wild type LF (LF-A) by the addition of two residues (His-Met) to the native Ala (A) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. We hypothesized that the "N-end rule", which relates the half-life of proteins in cells to the identity of their N-terminal residue, might be operative in the case of LF, so that the N-terminal residue of LF would determine the cytosolic stability and thereby the potency of LF. Mutational studies that replaced the native N-terminal residue of LF with known N-end rule stabilizing or destabilizing residues confirmed that the N-terminal residue plays a significant role in determining the potency of LT for cultured cells and experimental animals. The fact that a commercially-available LF preparation (LF-HMA) that is widely used in basic research studies and for evaluation of vaccines and therapeutics is 3-fold less potent than native LF (LF-A) should be considered when comparing published studies and in the design of future experiments.

Indexed as

Amino AcidsAnimalsAnthraxAntigens, BacterialBacterial ToxinsCHO CellsCricetinaeCricetulusFactor XaFemaleMAP Kinase Signaling SystemMiceProtein BindingProtein Structure, TertiaryRatsRats, Inbred F344Amino Acidsanthrax toxinAntigens, BacterialBacterial ToxinsFactor XaZinc

Identifiers

PMID18769623
PMCPMC2518864

What OpenQuestion holds

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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.