Evidence map›Paper›PMID 30618116›Full record

ArticleChembiochem : a European journal of chemical biology2019

Allele-Specific Inhibition of Histone Demethylases.

Shana Wagner, Megan Waldman, Simran Arora, Sinan Wang, Valerie Scott, Kabirul Islam

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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.

Shana WagnerDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Megan WaldmanDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Simran AroraDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Sinan WangDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Valerie ScottDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Kabirul IslamDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.ORCID 0000-0002-8680-6130

Funding

Site-Specific Photochemistry on Epigenetic Readers for Interactome ProfilingR01GM123234 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ISLAM, KABIRUL · 2017 to 2021
$1.5M
NIGMS NIH HHS R01 GM123234
6 · The paper itself

Abstract

Histone demethylases play a critical role in mammalian gene expression by removing methyl groups from lysine residues in degree- and site-specific manner. To specifically interrogate members and isoforms of this class of enzymes, we have developed demethylase variants with an expanded active site. The mutant enzymes are capable of performing lysine demethylation with wild-type proficiency, but are sensitive to inhibition by cofactor-competitive molecules embellished with a complementary steric "bump". The selected inhibitors show more than 20-fold selectivity over the wild-type demethylase, thus overcoming issues typical to pharmacological and genetic approaches. The mutant-inhibitor pairs are shown to act on a physiologically relevant full-length substrate. By engineering a conserved amino acid to achieve member-specific perturbation, this study provides a general approach for studying histone demethylases in diverse cellular processes.

Indexed as

Amino AcidsBiocatalysisCatalytic DomainDemethylationEnzyme InhibitorsHistonesHumansJumonji Domain-Containing Histone DemethylasesMolecular StructureMutationOxalatesProtein EngineeringSubstrate SpecificityAmino AcidsEnzyme InhibitorsHistonesJumonji Domain-Containing Histone DemethylasesKDM4A protein, humanOxalatesbump-and-holeepigeneticshistone demethylaseprotein engineeringsmall molecule inhibition

Identifiers

PMID30618116
PMCPMC6570502

What OpenQuestion holds

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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.