Evidence map›Paper›PMID 25372673›Full record

ArticleActa crystallographica. Section D, Biological crystallography2014

Anthrax toxin lethal factor domain 3 is highly mobile and responsive to ligand binding.

Kimberly M Maize, Elbek K Kurbanov, Teresa De La Mora-Rey, Todd W Geders, Dong Jin Hwang, Michael A Walters, Rodney L Johnson, Elizabeth A Amin, Barry C Finzel

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta crystallographica. Section D, Biological crystallography, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

4 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Inhibitors of the Metalloproteinase Anthrax Lethal Factor.Current topics in medicinal chemistry · 2016
    Review
  4. 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

9 authors at 1 institution in 1 country.

Kimberly M MaizeDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Elbek K KurbanovDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Teresa De La Mora-ReyDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Todd W GedersDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Dong Jin HwangDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Michael A WaltersDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Rodney L JohnsonDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Elizabeth A AminDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Barry C FinzelDepartment of Medicinal Chemistry and Minnesota Supercomputing Institute, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
University of Minnesota · US

Funding

Chemistry-Biology Interface Training GrantT32GM008700 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DISTEFANO, MARK D · 1999 to 2018
$4.0M
Anthrax Toxin Lethal Factor Inhibition StudyR01AI083234 · NIAID · UNIVERSITY OF MINNESOTA · PI AMBROSE, ELIZABETH ANN · 2009 to 2012
$1.9M
NIAID NIH HHS R01 AI083234NIGMS NIH HHS 5T32-GM008700NIGMS NIH HHS T32 GM008700
6 · The paper itself

Abstract

The secreted anthrax toxin consists of three components: the protective antigen (PA), edema factor (EF) and lethal factor (LF). LF, a zinc metalloproteinase, compromises the host immune system primarily by targeting mitogen-activated protein kinase kinases in macrophages. Peptide substrates and small-molecule inhibitors bind LF in the space between domains 3 and 4 of the hydrolase. Domain 3 is attached on a hinge to domain 2 via residues Ile300 and Pro385, and can move through an angular arc of greater than 35° in response to the binding of different ligands. Here, multiple LF structures including five new complexes with co-crystallized inhibitors are compared and three frequently populated LF conformational states termed `bioactive', `open' and `tight' are identified. The bioactive position is observed with large substrate peptides and leaves all peptide-recognition subsites open and accessible. The tight state is seen in unliganded and small-molecule complex structures. In this state, domain 3 is clamped over certain substrate subsites, blocking access. The open position appears to be an intermediate state between these extremes and is observed owing to steric constraints imposed by specific bound ligands. The tight conformation may be the lowest-energy conformation among the reported structures, as it is the position observed with no bound ligand, while the open and bioactive conformations are likely to be ligand-induced.

Indexed as

AnthraxAntigens, BacterialBacillus anthracisBacterial ToxinsBinding SitesCrystallography, X-RayDrug DesignHumansLigandsMetalloendopeptidasesModels, MolecularPeptidesProtein ConformationProtein Structure, TertiarySulfonamidesanthrax toxinAntigens, BacterialBacterial ToxinsLigandsMetalloendopeptidasesPeptidesSulfonamidesanthrax toxin lethal factorzinc metallproteinase

Identifiers

PMID25372673
PMCPMC4220970
OpenAlexW2051543221

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.