Evidence map›Paper›PMID 39019034›Full record

ArticleStructure (London, England : 1993)2024

Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.

Zahra Batool, Julia A Pavlova, Madhura N Paranjpe, Andrey G Tereshchenkov, Dmitrii A Lukianov, Ilya A Osterman, Alexey A Bogdanov, Natalia V Sumbatyan, Yury S Polikanov

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

9 authors.

Zahra BatoolDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Julia A PavlovaDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.
Madhura N ParanjpeDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Andrey G TereshchenkovDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.
Dmitrii A LukianovDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia.
Ilya A OstermanDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia.
Alexey A BogdanovDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Natalia V SumbatyanDepartment of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia. Electronic address: sumbtyan@belozersky.msu.ru.
Yury S PolikanovDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA; Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA; Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA. Electronic address: yuryp@uic.edu.

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Molecular mechanisms of action of ribosome-targeting antibiotics.R01GM132302 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI POLIKANOV, YURY · 2019 to 2022
$1.3M
NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM132302NIH HHS S10 OD021527
6 · The paper itself

Abstract

Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome. Crystal structure analysis reveals that the bulky berberine group folds into the P site of the peptidyl transferase center (PTC), where it competes with the formyl-methionine residue of the initiator tRNA. Our toe-printing data confirm that CAM-BER acts as a translation initiation inhibitor in stark contrast to CHL, a translation elongation inhibitor. Moreover, CAM-BER induces a distinct rearrangement of conformationally restrained nucleotide A2059, suggesting that the 23S rRNA plasticity is significantly higher than previously thought. CAM-BER shows potential in avoiding CHL resistance and presents opportunities for developing novel berberine derivatives of CHL through medicinal chemistry exploration.

Indexed as

BerberineChloramphenicolRibosomesAnti-Bacterial AgentsBinding SitesCrystallography, X-RayEscherichia coliModels, MolecularNucleic Acid ConformationPeptidyl TransferasesProtein BiosynthesisRNA, Ribosomal, 23SAnti-Bacterial AgentsBerberineChloramphenicolPeptidyl TransferasesRNA, Ribosomal, 23SaffinityantibioticberberinechloramphenicolNPETPTCribosometranslation inhibitorX-ray

Identifiers

PMID39019034
PMCPMC11380584

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.