Evidence map›Paper›PMID 27528683›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold.

Patricia R Feliciano, Catherine L Drennan, M Cristina Nonato

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Women in science symposium.Biophysical reviews · 2021
    Article
  9. A combination of Class-I fumarases and metabolites (α-ketoglutarate and fumarate) signal the DNA damage response inProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Article
  11. Article
  12. Biochemical characterization and essentiality ofThe Journal of biological chemistry · 2018
    Article
  13. 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

3 authors at 2 institutions in 2 countries.

Patricia R FelicianoLaboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo 14040-903, Brazil; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;ORCID 0000-0003-3853-115X
Catherine L DrennanDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139 cdrennan@mit.edu cristy@fcfrp.usp.br.
M Cristina NonatoLaboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo 14040-903, Brazil; cdrennan@mit.edu cristy@fcfrp.usp.br.
Universidade de São Paulo · BRHoward Hughes Medical Institute · US

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
NCRR NIH HHS S10 RR029205NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

Fumarate hydratases (FHs) are essential metabolic enzymes grouped into two classes. Here, we present the crystal structure of a class I FH, the cytosolic FH from Leishmania major, which reveals a previously undiscovered protein fold that coordinates a catalytically essential [4Fe-4S] cluster. Our 2.05 Å resolution data further reveal a dimeric architecture for this FH that resembles a heart, with each lobe comprised of two domains that are arranged around the active site. Besides the active site, where the substrate S-malate is bound bidentate to the unique iron of the [4Fe-4S] cluster, other binding pockets are found near the dimeric enzyme interface, some of which are occupied by malonate, shown here to be a weak inhibitor of this enzyme. Taken together, these data provide a framework both for investigations of the class I FH catalytic mechanism and for drug design aimed at fighting neglected tropical diseases.

Indexed as

Amino Acid MotifsCatalytic DomainCloning, MolecularCrystallography, X-RayEscherichia coliFumarate HydrataseGene ExpressionGenetic VectorsIron-Sulfur ProteinsLeishmania majorMalatesModels, MolecularProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein FoldingFumarate HydrataseIron-Sulfur ProteinsMalatesmalic acidProtozoan ProteinsRecombinant ProteinsFe-S clusterfumarate hydrataseleishmaniasesX-ray crystallography

Identifiers

PMID27528683
PMCPMC5024648
OpenAlexW2511929142

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.