Evidence map›Paper›PMID 30242198›Full record

ArticleScientific reports2018

Heme-dependent Inactivation of 5-Aminolevulinate Synthase from Caulobacter crescentus.

Hiroko Ikushiro, Atsushi Nagami, Tomoko Takai, Taiki Sawai, Yuki Shimeno, Hiroshi Hori, Ikuko Miyahara, Nobuo Kamiya, Takato Yano

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

15 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. A reversible feedback mechanism regulating mitochondrial heme synthesis.bioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022
    Review
  10. Article
  11. Review
  12. Using Diatom and Apicomplexan Models to Study the Heme Pathway ofInternational journal of molecular sciences · 2021
    Article
  13. Article
  14. Article
  15. 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 3 institutions in 1 country.

Hiroko IkushiroDepartment of Biochemistry, Faculty of Medicine, Osaka Medical College, Osaka, 569-8686, Japan. ikushiro@osaka-med.ac.jp.
Atsushi NagamiDepartment of Chemistry, Graduate School of Science, Osaka City University, Osaka, 558-8585, Japan.
Tomoko TakaiDepartment of Biochemistry, Faculty of Medicine, Osaka Medical College, Osaka, 569-8686, Japan.
Taiki SawaiDepartment of Biochemistry, Faculty of Medicine, Osaka Medical College, Osaka, 569-8686, Japan.
Yuki ShimenoDepartment of Chemistry, Graduate School of Science, Osaka City University, Osaka, 558-8585, Japan.
Hiroshi HoriDepartment of Chemistry, Graduate School of Science, Kobe University, Kobe, 657-8501, Japan.
Ikuko MiyaharaDepartment of Chemistry, Graduate School of Science, Osaka City University, Osaka, 558-8585, Japan.ORCID 0000-0002-0968-0343
Nobuo KamiyaDepartment of Chemistry, Graduate School of Science, Osaka City University, Osaka, 558-8585, Japan.
Takato YanoDepartment of Biochemistry, Faculty of Medicine, Osaka Medical College, Osaka, 569-8686, Japan. med013@osaka-med.ac.jp.
Osaka City University · JPOsaka Medical and Pharmaceutical University · JPKobe University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The biosynthesis of heme is strictly regulated, probably because of the toxic effects of excess heme and its biosynthetic precursors. In many organisms, heme biosynthesis starts with the production of 5-aminolevulinic acid (ALA) from glycine and succinyl-coenzyme A, a process catalyzed by a homodimeric enzyme, pyridoxal 5'-phosphate (PLP)-dependent 5-aminolevulinate synthase (ALAS). ALAS activity is negatively regulated by heme in various ways, such as the repression of ALAS gene expression, degradation of ALAS mRNA, and inhibition of mitochondrial translocation of the mammalian precursor protein. There has been no clear evidence, however, that heme directly binds to ALAS to negatively regulate its activity. We found that recombinant ALAS from Caulobacter crescentus was inactivated via a heme-mediated feedback manner, in which the essential coenzyme PLP was rel eased to form the inactive heme-bound enzyme. The spectroscopic properties of the heme-bound ALAS showed that a histidine-thiolate hexa-coordinated ferric heme bound to each subunit with a one-to-one stoichiometry. His340 and Cys398 were identified as the axial ligands of heme, and mutant ALASs lacking either of these ligands became resistant to heme-mediated inhibition. ALAS expressed in C. crescentus was also found to bind heme, suggesting that heme-mediated feedback inhibition of ALAS is physiologically relevant in C. crescentus.

Indexed as

5-Aminolevulinate SynthetaseAmino Acid SequenceBacterial ProteinsCaulobacter crescentusCoenzymesHemeHistidineHumansLigandsPyridoxal PhosphateRNA, Messenger5-Aminolevulinate SynthetaseBacterial ProteinsCoenzymesHemeHistidineLigandsPyridoxal PhosphateRNA, Messenger

Identifiers

PMID30242198
PMCPMC6154995
OpenAlexW2889868737

What OpenQuestion holds

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Registered trials

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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.