Evidence map›Paper›PMID 26805589›Full record

ArticleScientific reports2016

Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis.

Hyung-Seop Youn, Tae Gyun Kim, Mun-Kyoung Kim, Gil Bu Kang, Jung Youn Kang, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Youngjin Lee, Young Jun Im and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Quinolinic acid metabolism may mitigate AKI to CKD transition.bioRxiv : the preprint server for biology · 2025
    Article
  6. Review
  7. Review
  8. Structure, mechanism and inhibition of anthranilate phosphoribosyltransferase.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  9. Review
  10. Roles of NADInternational journal of molecular sciences · 2022
    Review
  11. NADAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2022
    Review
  12. Article
  13. Article
  14. NAD metabolism in aging and cancer.Experimental biology and medicine (Maywood, N.J.) · 2020
    Article
  15. NADSignal transduction and targeted therapy · 2020
    Review
  16. Article
  17. Targeting NADMolecular cancer research : MCR · 2020
    Article
  18. Article
  19. Macrophage de novo NADNature immunology · 2019
    Article
  20. 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

12 authors at 2 institutions in 1 country.

Hyung-Seop YounSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Tae Gyun KimSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Mun-Kyoung KimSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Gil Bu KangSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Jung Youn KangSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Jung-Gyu LeeSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Jun Yop AnSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Kyoung Ryoung ParkSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Youngjin LeeSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Young Jun ImCollege of Pharmacy, Chonnam National University, Gwangju 500-757, South Korea.
Jun Hyuck LeeDivision of Polar Life Sciences, Korea Polar Research Institute, Incheon 406-840, South Korea.
Soo Hyun EomSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
Gwangju Institute of Science and Technology · KRChonnam National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Quinolinate phosphoribosyltransferase (QPRT) catalyses the production of nicotinic acid mononucleotide, a precursor of de novo biosynthesis of the ubiquitous coenzyme nicotinamide adenine dinucleotide. QPRT is also essential for maintaining the homeostasis of quinolinic acid in the brain, a possible neurotoxin causing various neurodegenerative diseases. Although QPRT has been extensively analysed, the molecular basis of the reaction catalysed by human QPRT remains unclear. Here, we present the crystal structures of hexameric human QPRT in the apo form and its complexes with reactant or product. We found that the interaction between dimeric subunits was dramatically altered during the reaction process by conformational changes of two flexible loops in the active site at the dimer-dimer interface. In addition, the N-terminal short helix α1 was identified as a critical hexamer stabilizer. The structural features, size distribution, heat aggregation and ITC studies of the full-length enzyme and the enzyme lacking helix α1 strongly suggest that human QPRT acts as a hexamer for cooperative reactant binding via three dimeric subunits and maintaining stability. Based on our comparison of human QPRT structures in the apo and complex forms, we propose a drug design strategy targeting malignant glioma.

Indexed as

CatalysisCrystallography, X-RayDimerizationDrug DesignGliomaHumansNADNicotinate-Nucleotide Diphosphorylase (Carboxylating)PentosyltransferasesProtein Conformation, alpha-HelicalNADNicotinate-Nucleotide Diphosphorylase (Carboxylating)Pentosyltransferases

Identifiers

PMID26805589
PMCPMC4726147
OpenAlexW2419402284

What OpenQuestion holds

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LicenceCC BY
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.