Evidence map›Paper›PMID 38599294›Full record

ArticleBioorganic & medicinal chemistry letters2024

The mechanism of covalent inhibition of LAR phosphatase by illudalic acid.

Daniel T Hansen, Nicole J Rueb, Nathan D Levinzon, Thomas E Cheatham, Robert Gaston, Kh Tanvir Ahmed, Sandra Osburn-Staker, James E Cox, Gregory B Dudley, Amy M Barrios

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 46% 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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.

Daniel T HansenDepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Nicole J RuebDepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Nathan D LevinzonDepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Thomas E CheathamDepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Robert GastonC. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA.
Kh Tanvir AhmedC. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA.
Sandra Osburn-StakerMass Spectrometry and Proteomics Facility, University of Utah, Salt Lake City, UT 84112, USA.
James E CoxMass Spectrometry and Proteomics Facility, University of Utah, Salt Lake City, UT 84112, USA.
Gregory B DudleyC. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA.
Amy M BarriosDepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: amy.barrios@utah.edu.
University of Utah · USWest Virginia University · US

Funding

Biomolecular simulation for the end-stage refinement of nucleic acid structureR01GM081411 · NIGMS · UNIVERSITY OF UTAH · PI CHEATHAM, THOMAS E. · 2008 to 2022
$2.7M
Chemical Probes of Protein Tyrosine Phosphatase ActivityR01GM135295 · NIGMS · UNIVERSITY OF UTAH · PI BARRIOS, AMY M · 2019 to 2022
$1.2M
Q-ToF Mass Spectrometer for the University of Utah MS and Proteomics CoreS10OD018210 · OD · UNIVERSITY OF UTAH · PI COX, JAMES ERIC · 2015 to 2015
$530k
Chemical synthesis of illudalic acid analogs for stimulant use disorderR15DA056843 · NIDA · WEST VIRGINIA UNIVERSITY · PI DUDLEY, GREGORY B · 2022 to 2022
$380k
NIDA NIH HHS R15 DA056843NIGMS NIH HHS R01 GM081411NIGMS NIH HHS R01 GM135295NIH HHS S10 OD018210
6 · The paper itself

Abstract

Leukocyte antigen-related (LAR) phosphatase is a receptor-type protein tyrosine phosphatase involved in cellular signaling and associated with human disease including cancer and metabolic disorders. Selective inhibition of LAR phosphatase activity by well characterized and well validated small molecules would provide key insights into the roles of LAR phosphatase in health and disease, but identifying selective inhibitors of LAR phosphatase activity has been challenging. Recently, we described potent and selective inhibition of LAR phosphatase activity by the fungal natural product illudalic acid. Here we provide a detailed biochemical characterization of the adduct formed between LAR phosphatase and illudalic acid. A mass spectrometric analysis indicates that two cysteine residues are covalently labeled by illudalic acid and a related analog. Mutational analysis supports the hypothesis that inhibition of LAR phosphatase activity is due primarily to the adduct with the catalytic cysteine residue. A computational study suggests potential interactions between the illudalic acid moiety and the enzyme active site. Taken together, these data offer novel insights into the mechanism of inhibition of LAR phosphatase activity by illudalic acid.

Indexed as

CoumarinsReceptor-Like Protein Tyrosine Phosphatases, Class 2CysteineHumansCoumarinsCysteineilludalic acidReceptor-Like Protein Tyrosine Phosphatases, Class 2Covalent inhibitorsEnzyme inhibitionLAR PTPProtein tyrosine phosphatases

Identifiers

PMID38599294
PMCPMC11057956
OpenAlexW4394611801

What OpenQuestion holds

Textmetadata
LicenceTDM
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.