Evidence map›Paper›PMID 31128421›Full record

ArticleMolecular therapy. Nucleic acids2019

Characterization of G-Quadruplex Motifs in espB, espK, and cyp51 Genes of Mycobacterium tuberculosis as Potential Drug Targets.

Subodh Kumar Mishra, Uma Shankar, Neha Jain, Kriti Sikri, Jaya Sivaswami Tyagi, Tarun Kumar Sharma, Jean-Louis Mergny, Amit Kumar

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 56 citations in OpenAlex.

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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 at 4 institutions in 3 countries.

Subodh Kumar MishraDiscipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, Indore 453552, India.
Uma ShankarDiscipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, Indore 453552, India.
Neha JainDiscipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, Indore 453552, India.
Kriti SikriDepartment of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India.
Jaya Sivaswami TyagiDepartment of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India.
Tarun Kumar SharmaCentre for Bio-design and Diagnostics, Translational Health Science and Technology Institute, Faridabad, Haryana 121001, India.
Jean-Louis MergnyARNA Laboratory, INSERM U1212, CNRS UMR 5320, Université de Bordeaux, Bordeaux, France; Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
Amit KumarDiscipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, Indore 453552, India. Electronic address: amitk@iiti.ac.in.
Indian Institute of Technology Indore · INDepartment of Biotechnology · INCentre National de la Recherche Scientifique · FRTranslational Health Science and Technology Institute · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

G-quadruplex structure forming motifs are among the most studied evolutionarily conserved drug targets that are present throughout the genome of different organisms and susceptible to influencing various biological processes. Here we report highly conserved potential G-quadruplex motifs (PGQs) in three essential genes (espK, espB, and cyp51) among 160 strains of the Mycobacterium tuberculosis genome. Products of these genes are involved in pathways that are responsible for virulence determination of bacteria inside the host cell and its survival by maintaining membrane fluidity. The espK and espB genes are essential players that prevent the formation of mature phagolysosome and antigen presentation by host macrophages. The cyp51 is another PGQ-possessing gene involved in sterol biosynthesis pathway and membrane formation. In the present study, we revealed the formation of stable intramolecular parallel G-quadruplex structures by Mycobacterium PGQs using a combination of techniques (NMR, circular dichroism [CD], and gel electrophoresis). Next, isothermal titration calorimetry (ITC) and CD melting analysis demonstrated that a well-known G-quadruplex ligand, TMPyP4, binds to and stabilizes these PGQ motifs. Finally, polymerase inhibition and qRT-PCR assays highlight the biological relevance of PGQ-possessing genes in this pathogen and demonstrate that G-quadruplexes are potential drug targets for the development of effective anti-tuberculosis therapeutics.

Indexed as

anti-tuberculosis compoundsdrug targetsG-quadruplexG-quadruplex binderG-quadruplex mediated inhibitionMycobacterium tuberculosis

Identifiers

PMID31128421
PMCPMC6531831
OpenAlexW2943089509

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.