ArticleChemistry & biology2010
Application of fragment-based drug discovery to membrane proteins: identification of ligands of the integral membrane enzyme DsbB.
Article in Chemistry & biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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.
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.
Who cites it
28 citing papers in PubMed.
- The Nature of Nanodisc Lipids Influences Fragment-Based Drug Discovery Results.Chemical biology & drug design · 2025Article
- Optimizing NMR fragment-based drug screening for membrane protein targets.Journal of structural biology: X · 2024Article
- Do Nanodisc Assembly Conditions Affect Natural Lipid Uptake?Journal of the American Society for Mass Spectrometry · 2023Article
- Fragment-based screening by protein-detected NMR spectroscopy.Methods in enzymology · 2023Article
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
- Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials.ChemMedChem · 2022Article
- Antivirulence DsbA inhibitors attenuateFASEB bioAdvances · 2021Article
- Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021Review
- Anti-Virulence Therapeutic Approaches forAntibiotics (Basel, Switzerland) · 2021Review
- A high-throughput cell-based assay pipeline for the preclinical development of bacterial DsbA inhibitors as antivirulence therapeutics.Scientific reports · 2021Article
- Protein Disulfide Exchange by the Intramembrane Enzymes DsbB, DsbD, and CcdA.Journal of molecular biology · 2020Review
- The Fragment-Based Development of a Benzofuran Hit as a New Class ofMolecules (Basel, Switzerland) · 2019Article
- Virulence of the Melioidosis Pathogen Burkholderia pseudomallei Requires the Oxidoreductase Membrane Protein DsbB.Infection and immunity · 2018Article
- Disulfide bond formation in prokaryotes.Nature microbiology · 2018Review
- Bacterial thiol oxidoreductases - from basic research to new antibacterial strategies.Applied microbiology and biotechnology · 2017Review
- Nanodiscs in Membrane Biochemistry and Biophysics.Chemical reviews · 2017Review
- SPR-based fragment screening with neurotensin receptor 1 generates novel small molecule ligands.PloS one · 2017Article
- Biophysics in drug discovery: impact, challenges and opportunities.Nature reviews. Drug discovery · 2016Review
- Targeting Bacterial Dsb Proteins for the Development of Anti-Virulence Agents.Molecules (Basel, Switzerland) · 2016Review
- ACFIS: a web server for fragment-based drug discovery.Nucleic acids research · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Membrane proteins are important pharmaceutical targets, but they pose significant challenges for fragment-based drug discovery approaches. Here, we present the first successful use of biophysical methods to screen for fragment ligands to an integral membrane protein. The Escherichia coli inner membrane protein DsbB was solubilized in detergent micelles and lipid bilayer nanodiscs. The solubilized protein was immobilized with retention of functionality and used to screen 1071 drug fragments for binding using target immobilized NMR Screening. Biochemical and biophysical validation of the eight most potent hits revealed an IC(50) range of 7-200 microM. The ability to insert a broad array of membrane proteins into nanodiscs, combined with the efficiency of TINS, demonstrates the feasibility of finding fragments targeting membrane proteins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.