Evidence map›Paper›PMID 33206666›Full record

ArticlePloS one2020

Biophysical and X-ray structural studies of the (GGGTT)3GGG G-quadruplex in complex with N-methyl mesoporphyrin IX.

Linda Yingqi Lin, Sawyer McCarthy, Barrett M Powell, Yanti Manurung, Irene M Xiang, William L Dean, Brad Chaires, Liliya A Yatsunyk

Abstract read
In one paragraph

Article in PloS one, 2020. 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
–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

13 citing papers in PubMed.

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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

8 authors.

Linda Yingqi LinDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.ORCID 0000-0001-5011-1305
Sawyer McCarthyDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.ORCID 0000-0002-1063-1784
Barrett M PowellDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.
Yanti ManurungDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.
Irene M XiangDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.
William L DeanStructural Biology Program JG Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America.
Brad ChairesStructural Biology Program JG Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America.
Liliya A YatsunykDepartment of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania, United States of America.ORCID 0000-0003-3946-0939

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI MALCOLM S. CAPEL · 2018 to 2026
$34.2M
Targeting Nucleic Acids with an Integrated Vitural and Actual ScreenR01GM077422 · NIGMS · UNIVERSITY OF LOUISVILLE · PI CHAIRES, JONATHAN B., TRENT, JOHN O · 2007 to 2020
$3.7M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Deciphering the structure and dynamics of quadruplex DNA and DNA-ligand complexesR15CA208676 · NCI · SWARTHMORE COLLEGE · PI YATSUNYK, LILIYA A · 2017 to 2017
$411k
NCI NIH HHS R15 CA208676NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM077422NIH HHS S10 OD021527
6 · The paper itself

Abstract

The G-quadruplex (GQ) is a well-studied non-canonical DNA structure formed by G-rich sequences found at telomeres and gene promoters. Biological studies suggest that GQs may play roles in regulating gene expression, DNA replication, and DNA repair. Small molecule ligands were shown to alter GQ structure and stability and thereby serve as novel therapies, particularly against cancer. In this work, we investigate the interaction of a G-rich sequence, 5'-GGGTTGGGTTGGGTTGGG-3' (T1), with a water-soluble porphyrin, N-methyl mesoporphyrin IX (NMM) via biophysical and X-ray crystallographic studies. UV-vis and fluorescence titrations, as well as a Job plot, revealed a 1:1 binding stoichiometry with an impressively tight binding constant of 30-50 μM-1 and ΔG298 of -10.3 kcal/mol. Eight extended variants of T1 (named T2 -T9) were fully characterized and T7 was identified as a suitable candidate for crystallographic studies. We solved the crystal structures of the T1- and T7-NMM complexes at 2.39 and 2.34 Å resolution, respectively. Both complexes form a 5'-5' dimer of parallel GQs capped by NMM at the 3' G-quartet, supporting the 1:1 binding stoichiometry. Our work provides invaluable details about GQ-ligand binding interactions and informs the design of novel anticancer drugs that selectively recognize specific GQs and modulate their stability for therapeutic purposes.

Indexed as

Biophysical PhenomenaArea Under CurveBase SequenceCrystallography, X-RayG-QuadruplexesMesoporphyrinsModels, MolecularSpectrometry, FluorescenceSpectrophotometry, UltravioletThermodynamicsmesoporphyrin IXMesoporphyrins

Identifiers

PMID33206666
PMCPMC7673559

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.