Evidence map›Paper›PMID 36964942›Full record

ArticleChembiochem : a European journal of chemical biology2023

Chemoproteomic Profiling Reveals that Anticancer Natural Product Dankastatin B Covalently Targets Mitochondrial VDAC3.

Bridget P Belcher, Paulo A Machicao, Binqi Tong, Emily Ho, Julia Friedli, Brian So, Helen Bui, Yosuke Isobe, Thomas J Maimone, Daniel K Nomura

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Expression and prognostic impact ofTranslational cancer research · 2024
    Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Bridget P BelcherDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Paulo A MachicaoDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Binqi TongDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Emily HoDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Julia FriedliDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Brian SoDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Helen BuiDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Yosuke IsobeDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Thomas J MaimoneDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.
Daniel K NomuraDepartment of Chemistry, University of California-Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0003-1614-8360
Innovative Genomics Institute · USUniversity of California, Berkeley · US

Funding

Tackling Undruggable Cancer Targets using Chemoproteomic PlatformsR35CA263814 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Daniel Nomura · 2022 to 2026
$4.6M
Chemical Synthesis and Biology of Complex AlkaloidsR01GM136945 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MAIMONE, THOMAS JOHN, NOMURA, DANIEL · 2020 to 2023
$2.0M
NCI NIH HHS R35 CA263814NIH HHS R01GM136945
6 · The paper itself

Abstract

Chlorinated gymnastatin and dankastatin alkaloids derived from the fungal strain Gymnascella dankaliensis have been reported to possess significant anticancer activity but their mode of action is unknown. These members possess electrophilic functional groups that can might undergo covalent bond formation with specific proteins to exert their biological activity. To better understand the mechanism of action of this class of natural products, we mapped the proteome-wide cysteine reactivity of the most potent of these alkaloids, dankastatin B, by using activity-based protein profiling chemoproteomic approaches. We identified a primary target of dankastatin B in breast cancer cells as cysteine C65 of the voltage-dependent anion-selective channel on the outer mitochondrial membrane VDAC3. We demonstrated direct and covalent interaction of dankastatin B with VDAC3. VDAC3 knockdown conferred hypersensitivity to dankastatin B-mediated antiproliferative effects in breast cancer cells, thus indicating that VDAC3 was at least partially involved in the anticancer effects of this natural product. Our study reveals a potential mode of action of dankastatin B through covalent targeting of VDAC3 and highlights the utility of chemoproteomic approaches in gaining mechanistic understanding of electrophilic natural products.

Indexed as

Biological ProductsBreast NeoplasmsBenzopyransCysteineFemaleHumansMitochondriaMitochondrial Membrane Transport ProteinsVoltage-Dependent Anion ChannelsBenzopyransBiological ProductsCysteinedankastatin BMitochondrial Membrane Transport ProteinsVDAC3 protein, humanVoltage-Dependent Anion Channelsactivity-based protein profilingchemoproteomics, dankastatin Bgymnastatins, natural productsVDAC3

Identifiers

PMID36964942
OpenAlexW4360946591

What OpenQuestion holds

Textmetadata
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.