Evidence map›Paper›PMID 23445365›Full record

ArticleBiochemistry2013

Aging-associated enzyme human clock-1: substrate-mediated reduction of the diiron center for 5-demethoxyubiquinone hydroxylation.

Tsai-Te Lu, Seung Jae Lee, Ulf-Peter Apfel, Stephen J Lippard

Abstract read
In one paragraph

Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023
    Review
  4. Article
  5. Article
  6. Article
  7. Manganese-driven CoQ deficiency.Nature communications · 2022
    Article
  8. Article
  9. Article
  10. Coenzyme QEssays in biochemistry · 2018
    Review
  11. Biochemistry of Mitochondrial Coenzyme Q Biosynthesis.Trends in biochemical sciences · 2017
    Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  18. Electron transfer control in soluble methane monooxygenase.Journal of the American Chemical Society · 2014
    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

4 authors.

Tsai-Te LuDepartment of Chemistry, Massachusetts Institute of Technology , Cambridge, MA 02139, USA.
Seung Jae Lee
Ulf-Peter Apfel
Stephen J Lippard

Funding

NONHEME IRON AND THE BIOLOGICAL OXIDATION OF METHANER01GM032134 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LIPPARD, STEPHEN J. · 1985 to 2013
$6.9M
LIGAND-BRIDGED POLYNUCLEAR METAL COMPLEXES &PROTEINSR37GM032134 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LIPPARD, STEPHEN J · 1988 to 1997
–
NIGMS NIH HHS GM032134NIGMS NIH HHS R01 GM032134
6 · The paper itself

Abstract

The mitochondrial membrane-bound enzyme Clock-1 (CLK-1) extends the average longevity of mice and Caenorhabditis elegans, as demonstrated for Δclk-1 constructs for both organisms. Such an apparent impact on aging and the presence of a carboxylate-bridged diiron center in the enzyme inspired this work. We expressed a soluble human CLK-1 (hCLK-1) fusion protein with an N-terminal immunoglobulin binding domain of protein G (GB1). Inclusion of the solubility tag allowed for thorough characterization of the carboxylate-bridged diiron active site of the resulting GB1-hCLK-1 by spectroscopic and kinetic methods. Both UV-visible and Mössbauer experiments provide unambiguous evidence that GB1-hCLK-1 functions as a 5-demethoxyubiquinone-hydroxylase, utilizing its carboxylate-bridged diiron center. The binding of DMQn (n = 0 or 2) to GB1-hCLK-1 mediates reduction of the diiron center by nicotinamide adenine dinucleotide (NADH) and initiates O2 activation for subsequent DMQ hydroxylation. Deployment of DMQ to mediate reduction of the diiron center in GB1-hCLK-1 improves substrate specificity and diminishes consumption of NADH that is uncoupled from substrate oxidation. Both Vmax and kcat/KM for DMQ hydroxylation increase when DMQ0 is replaced by DMQ2 as the substrate, which demonstrates that an isoprenoid side chain enhances enzymatic hydroxylation and improves catalytic efficiency.

Indexed as

AgingBacterial ProteinsCatalytic DomainCLOCK ProteinsCloning, MolecularElectron TransportGene ExpressionHumansHydroxylationIron CompoundsKineticsOxygenasesProtein Structure, TertiaryRecombinant Fusion ProteinsSolubilityUbiquinoneBacterial ProteinsCLOCK ProteinsIgG Fc-binding protein, StreptococcusIron CompoundsOxygenasesRecombinant Fusion ProteinsUbiquinone

Identifiers

PMID23445365
PMCPMC3615049

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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.