Evidence map›Paper›PMID 33831386›Full record

ArticleClinical biochemistry2021

Generation and characterization of a laforin nanobody inhibitor.

Zoe R Simmons, Savita Sharma, Jeremiah Wayne, Sheng Li, Craig W Vander Kooi, Matthew S Gentry

Open access · greenAbstract read
In one paragraph

Article in Clinical biochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα.Proceedings of the National Academy of Sciences of the United States of America · 2022
    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

6 authors at 2 institutions in 1 country.

Zoe R SimmonsDepartment of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
Savita SharmaDepartment of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
Jeremiah WayneDepartment of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
Sheng LiDepartment of Medicine, University of California at San Diego, La Jolla, CA 92093, United States.
Craig W Vander KooiDepartment of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, United States; Lafora Epilepsy Cure Initiative, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
Matthew S GentryDepartment of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, United States; Lafora Epilepsy Cure Initiative, University of Kentucky College of Medicine, Lexington, KY 40536, United States. Electronic address: matthew.gentry@uky.edu.
University of Kentucky · USUniversity of California San Diego · US

Funding

Suppressing glycogen storage with small molecule inhibitors as a therapeutic approach to Lafora DiseaseP01NS097197 · NINDS · UNIVERSITY OF KENTUCKY · PI GAO, TIANYAN · 2016 to 2021
$9.0M
Brain Glycogen-Metabolism,Mechanisms, and Therapeutic PotentialR35NS116824 · NINDS · UNIVERSITY OF KENTUCKY · PI Matthew S. Gentry · 2020 to 2026
$8.2M
NRSA Training CoreTL1TR001997 · NCATS · UNIVERSITY OF KENTUCKY · PI PENDERGAST, JULIE S, STOOPS, WILLIAM WALTON · 2016 to 2025
$4.2M
NCATS NIH HHS TL1 TR001997NINDS NIH HHS P01 NS097197NINDS NIH HHS R35 NS116824
6 · The paper itself

Abstract

objectivesMutations in the gene encoding the glycogen phosphatase laforin result in the fatal childhood dementia Lafora disease (LD). A cellular hallmark of LD is cytoplasmic, hyper-phosphorylated, glycogen-like aggregates called Lafora bodies (LBs) that form in nearly all tissues and drive disease progression. Additional tools are needed to define the cellular function of laforin, understand the pathological role of laforin in LD, and determine the role of glycogen phosphate in glycogen metabolism. In this work, we present the generation and characterization of laforin nanobodies, with one being a laforin inhibitor. DESIGN AND

methodsWe identify multiple classes of specific laforin-binding nanobodies and determine their binding epitopes using hydrogen deuterium exchange (HDX) mass spectrometry. Using para-nitrophenyl phosphate (pNPP) and a malachite gold-based assay specific for glucan phosphatase activity, we assess the inhibitory effect of one nanobody on laforin's catalytic activity.

resultsSix families of laforin nanobodies are characterized and their epitopes mapped. One nanobody is identified and characterized that serves as an inhibitor of laforin's phosphatase activity.

conclusionsThe six generated and characterized laforin nanobodies, with one being a laforin inhibitor, are an important set of tools that open new avenues to define unresolved glycogen metabolism questions.

Indexed as

AnimalsBiological AssayCamelids, New WorldChromatography, GelEnzyme InhibitorsEpitope MappingGlycogenGoldHumansHydrogen Deuterium Exchange-Mass SpectrometryLafora DiseaseModels, MolecularNitrophenolsOrganometallic CompoundsOrganophosphorus CompoundsPhosphoric Monoester HydrolasesEnzyme InhibitorsEPM2A protein, humanGlycogenGoldmalachiteNitrophenolsnitrophenylphosphateOrganometallic CompoundsOrganophosphorus CompoundsPhosphoric Monoester HydrolasesProtein Tyrosine Phosphatases, Non-ReceptorSingle-Domain AntibodiesAmylopectinGlycogenLafora diseaseLaforinNanobodyPhosphatase

Identifiers

PMID33831386
PMCPMC8217207
OpenAlexW3146612134

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.