Evidence map›Paper›PMID 35446570›Full record

ArticleJournal of the American Chemical Society2022

Three Mutations Convert the Selectivity of a Protein Sensor from Nicotinic Agonists to S-Methadone for Use in Cells, Organelles, and Biofluids.

Anand K Muthusamy, Charlene H Kim, Scott C Virgil, Hailey J Knox, Jonathan S Marvin, Aaron L Nichols, Bruce N Cohen, Dennis A Dougherty, Loren L Looger, Henry A Lester

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Antidepressants enter cells, organelles, and membranes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Review
  3. Review
  4. Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  5. Review
  6. Article
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

10 authors at 2 institutions in 1 country.

Anand K MuthusamyDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91106, United States.ORCID 0000-0003-1041-914X
Charlene H KimDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91106, United States.
Scott C VirgilDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91106, United States.
Hailey J KnoxDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91106, United States.
Jonathan S MarvinHoward Hughes Medical Institute, Janelia Research Campus, Ashburn, Virginia 20147, United States.ORCID 0000-0003-2294-4515
Aaron L NicholsDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91106, United States.
Bruce N CohenDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91106, United States.
Dennis A DoughertyDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91106, United States.ORCID 0000-0003-1464-2461
Loren L LoogerHoward Hughes Medical Institute, University of California, San Diego, San Diego, California 92093, United States.
Henry A LesterDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91106, United States.
California Institute of Technology · USHoward Hughes Medical Institute · US

Funding

PREDOCTORAL TRAINING IN BIOLOGY AND CHEMISTRYT32GM007616 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI STERNBERG, PAUL WARREN · 1985 to 2019
$22.9M
Fluorescent biosensors for subcellular pharmacokineticsR01GM123582 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2016 to 2021
$3.8M
Predoctoral Training in Quantitative NeuroscienceT32NS105595 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI MARKUS MEISTER · 2019 to 2026
$2.6M
Purchase of a nanoLC-QTRAP Mass Spectrometer for Targeted Proteomics StudiesS10OD010788 · OD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HESS, SONJA · 2013 to 2013
$600k
Acquisition of a Q-Exactive Plus mass spectrometer.S10OD020013 · OD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HESS, SONJA · 2015 to 2015
$600k
Nicotine Inside NeuronsR21DA043829 · NIDA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2017 to 2018
$454k
Opioids inside OrganellesR21DA049140 · NIDA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2019 to 2020
$452k
NIDA NIH HHS R21 DA043829NIDA NIH HHS R21 DA049140NIGMS NIH HHS R01 GM123582NIGMS NIH HHS T32 GM007616NIH HHS S10 OD010788NIH HHS S10 OD020013NINDS NIH HHS T32 NS105595
6 · The paper itself

Abstract

We report a reagentless, intensity-based S-methadone fluorescent sensor, iS-methadoneSnFR, consisting of a circularly permuted GFP inserted within the sequence of a mutated bacterial periplasmic binding protein (PBP). We evolved a previously reported nicotine-binding PBP to become a selective S-methadone-binding sensor, via three mutations in the PBP's second shell and hinge regions. iS-methadoneSnFR displays the necessary sensitivity, kinetics, and selectivity─notably enantioselectivity against R-methadone─for biological applications. Robust iS-methadoneSnFR responses in human sweat and saliva and mouse serum enable diagnostic uses. Expression and imaging in mammalian cells demonstrate that S-methadone enters at least two organelles and undergoes acid trapping in the Golgi apparatus, where opioid receptors can signal. This work shows a straightforward strategy in adapting existing PBPs to serve real-time applications ranging from subcellular to personal pharmacokinetics.

Indexed as

Nicotinic AgonistsPeriplasmic Binding ProteinsAnimalsMammalsMethadoneMiceMutationOrganellesMethadoneNicotinic AgonistsPeriplasmic Binding Proteins

Identifiers

PMID35446570
PMCPMC9121368
OpenAlexW4226270664

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.