Evidence map›Paper›PMID 30150323›Full record

ArticleEMBO reports2018

Active site alanine mutations convert deubiquitinases into high-affinity ubiquitin-binding proteins.

Marie E Morrow, Michael T Morgan, Marcello Clerici, Katerina Growkova, Ming Yan, David Komander, Titia K Sixma, Michal Simicek, Cynthia Wolberger

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

41 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Widely Used CaMKII Regulatory Segment Mutations Cause Tight Actinin Binding and Dendritic Spine Enlargement in Unstimulated Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  5. Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7).Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Activation dynamics of ubiquitin-specific protease 7.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025
    Review
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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

9 authors at 4 institutions in 4 countries.

Marie E MorrowDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael T MorganDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Marcello ClericiDivision of Biochemistry and Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Katerina GrowkovaFaculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
Ming YanDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David KomanderMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-8092-4320
Titia K SixmaDivision of Biochemistry and Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Michal SimicekFaculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
Cynthia WolbergerDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA cwolberg@jhmi.edu.ORCID 0000-0001-8578-2969
Johns Hopkins University · USMRC Laboratory of Molecular Biology · GBThe Netherlands Cancer Institute · NLUniversity of Ostrava · CZ

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Structure and Function of the SAGA Deubiquitinating ModuleR01GM095822 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI WOLBERGER, CYNTHIA · 2011 to 2018
$2.7M
REGULATION OF UBIQUITINATION BY DUB-E2 UBIQUITIN CONJUGATING ENZYME COMPLEXESR01GM109102 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI WOLBERGER, CYNTHIA · 2014 to 2017
$1.9M
European Research Council 309756Medical Research Council MC_U105192732Medical Research Council U105192732NIGMS NIH HHS P41 GM103393NIGMS NIH HHS R01 GM095822NIGMS NIH HHS R01 GM109102
6 · The paper itself

Abstract

A common strategy for exploring the biological roles of deubiquitinating enzymes (DUBs) in different pathways is to study the effects of replacing the wild-type DUB with a catalytically inactive mutant in cells. We report here that a commonly studied DUB mutation, in which the catalytic cysteine is replaced with alanine, can dramatically increase the affinity of some DUBs for ubiquitin. Overexpression of these tight-binding mutants thus has the potential to sequester cellular pools of monoubiquitin and ubiquitin chains. As a result, cells expressing these mutants may display unpredictable dominant negative physiological effects that are not related to loss of DUB activity. The structure of the SAGA DUB module bound to free ubiquitin reveals the structural basis for the 30-fold higher affinity of Ubp8

Indexed as

AlanineAmino Acid SubstitutionCarrier ProteinsCatalysisCysteineDeubiquitinating EnzymesEndopeptidasesHumansMutationProtein ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTrans-ActivatorsUbiquitinUbiquitinationUbiquitin-Specific ProteasesAlanineCarrier ProteinsCysteineDeubiquitinating EnzymesEndopeptidasesSaccharomyces cerevisiae ProteinsSAGA complex, S cerevisiaeTrans-ActivatorsUbiquitinUbiquitin-Specific ProteasesUBP8 protein, S cerevisiaeUSP4 protein, humandeubiquitinating enzymepolyubiquitinubiquitin binding

Identifiers

PMID30150323
PMCPMC6172466
OpenAlexW2889126774

What OpenQuestion holds

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LicenceCC BY
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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.