Evidence map›Paper›PMID 19523496›Full record

ArticleMolecular and biochemical parasitology2009

Cross-species activation of trypanosome S-adenosylmethionine decarboxylase by the regulatory subunit prozyme.

Erin K Willert, Margaret A Phillips

Abstract read
In one paragraph

Article in Molecular and biochemical parasitology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022
    Review
  5. Polyamines in protozoan pathogens.The Journal of biological chemistry · 2018
    Review
  6. Review
  7. The Major Protein Arginine Methyltransferase inThe Journal of biological chemistry · 2017
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Current status of the polyamine research field.Methods in molecular biology (Clifton, N.J.) · 2011
    Review
  15. Article
  16. 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

2 authors at 1 institution in 1 country.

Erin K WillertDepartment of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
Margaret A Phillips
The University of Texas Southwestern Medical Center · US

Funding

MECHANISMS OF DRUG ACTION AND DISPOSITIONT32GM007062 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI MANGELSDORF, DAVID J · 1985 to 2020
$7.4M
TRYPANSOMIASIS--MOLECULAR APPROACHES TO CHEMOTHERAPYR01AI034432 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI PHILLIPS, MARGARET A. · 1995 to 2024
$4.9M
Polyamine and trypanothione metabolism in Trypanosoma bruceiR37AI034432 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI PHILLIPS, MARGARET A. · 2009 to 2018
$4.0M
NIAID NIH HHS R01 AI034432NIAID NIH HHS R01 AI34432NIAID NIH HHS R37 AI034432NIGMS NIH HHS GM 007062NIGMS NIH HHS T32 GM007062
6 · The paper itself

Abstract

The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease (American trypanosomiasis), a neglected disease of Central and South America. Polyamines are small organic cations that are required for cell growth and their biosynthesis has been the target of drug discovery efforts in both T. cruzi and the related Trypanosoma brucei parasites. Here we show that, as previously demonstrated for T. brucei, S-adenosylmethionine decarboxylase (AdoMetDC) from T. cruzi forms a heterodimer with prozyme, an inactive homolog that arose by gene duplication of the canonical enzyme uniquely in the trypanosomatids. The T. cruzi AdoMetDC/prozyme heterodimer is 110-fold more active than homodimeric AdoMetDC. Unlike for T. brucei AdoMetDC, the activity of the T. cruzi heterodimer is further stimulated by putrescine to generate an enzyme with similar catalytic efficiency to the fully activated T. brucei enzyme. The effects of prozyme on T. cruzi AdoMetDC are mediated by an increase in k(cat), while the predominant effect of putrescine is to lower the K(m). Finally we demonstrate that the cross-species heterodimers of T. cruzi and T. brucei AdoMetDC and prozyme pairs are functional, and that putrescine is required for prozyme to fully activate the mixed species heterodimers. These data demonstrate that prozyme mediated activation of AdoMetDC is a common mechanism required to regulate AdoMetDC activity in the trypanosomatids.

Indexed as

Adenosylmethionine DecarboxylaseAnimalsDimerizationEnzyme ActivatorsKineticsProtein SubunitsPutrescineTrypanosoma brucei bruceiTrypanosoma cruziAdenosylmethionine DecarboxylaseEnzyme ActivatorsProtein SubunitsPutrescine

Identifiers

PMID19523496
PMCPMC2730992
OpenAlexW2057604614

What OpenQuestion holds

Textmetadata
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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.