Evidence map›Paper›PMID 30626866›Full record

ArticleNature communications2019

Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling.

James E Longbotham, Cynthia M Chio, Venkatasubramanian Dharmarajan, Michael J Trnka, Idelisse Ortiz Torres, Devrishi Goswami, Karen Ruiz, Alma L Burlingame, Patrick R Griffin, Danica Galonić Fujimori

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 48 citations in OpenAlex.

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  6. Discovery and structural studies of histone demethylases.Frontiers in epigenetics and epigenomics · 2025
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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.

James E LongbothamDepartment of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA.
Cynthia M ChioDepartment of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA.
Venkatasubramanian DharmarajanDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Michael J TrnkaDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA.
Idelisse Ortiz TorresChemistry and Chemical Biology Graduate Program, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA.
Devrishi GoswamiDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Karen RuizTETRAD Graduate Program, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA.
Patrick R GriffinDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, 33458, USA.ORCID http://orcid.org/0000-0002-3404-690X
Danica Galonić FujimoriDepartment of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, CA, 94158, USA. Danica.Fujimori@ucsf.edu.
University of California, San Francisco · USScripps Research Institute · US

Funding

Allosteric Regulation in the KDM5 Family of Histone DemethylasesR01GM114044 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FUJIMORI, DANICA GALONIC · 2015 to 2018
$1.3M
NIGMS NIH HHS R01 GM114044NIH HHS 1S10D016229NIH HHS R01 GM114044NIH HHS R01 GM114044-03S1
6 · The paper itself

Abstract

Histone demethylase KDM5A removes methyl marks from lysine 4 of histone H3 and is often overexpressed in cancer. The in vitro demethylase activity of KDM5A is allosterically enhanced by binding of its product, unmodified H3 peptides, to its PHD1 reader domain. However, the molecular basis of this allosteric enhancement is unclear. Here we show that saturation of the PHD1 domain by the H3 N-terminal tail peptides stabilizes binding of the substrate to the catalytic domain and improves the catalytic efficiency of demethylation. When present in saturating concentrations, differently modified H3 N-terminal tail peptides have a similar effect on demethylation. However, they vary greatly in their affinity towards the PHD1 domain, suggesting that H3 modifications can tune KDM5A activity. Furthermore, hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) experiments reveal conformational changes in the allosterically enhanced state. Our findings may enable future development of anti-cancer therapies targeting regions involved in allosteric regulation.

Indexed as

AnimalsCatalytic DomainHistonesModels, MolecularProtein ConformationProtein DomainsRetinoblastoma-Binding Protein 2Sf9 CellsHistonesKDM5A protein, humanRetinoblastoma-Binding Protein 2

Identifiers

PMID30626866
PMCPMC6327041
OpenAlexW2910126306

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.