Evidence map›Paper›PMID 20357770›Full record

ArticleNature structural & molecular biology2010

A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain.

John Wojcik, Oliver Hantschel, Florian Grebien, Ines Kaupe, Keiryn L Bennett, John Barkinge, Richard B Jones, Akiko Koide, Giulio Superti-Furga, Shohei Koide

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

99 citing papers in PubMed, 167 citations in OpenAlex.

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  13. Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.Proceedings of the National Academy of Sciences of the United States of America · 2022
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39 more citing papers are in PubMed but not listed here.

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 2 countries.

John WojcikDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
Oliver Hantschel
Florian Grebien
Ines Kaupe
Keiryn L Bennett
John Barkinge
Richard B Jones
Akiko Koide
Giulio Superti-Furga
Shohei Koide
Austrian Academy of Sciences · ATUniversity of Chicago · US

Funding

MEDICAL SCIENTIST TRAININGT32GM007281 · NIGMS · UNIVERSITY OF CHICAGO · PI CLARK, MARCUS RAMSAY · 1985 to 2022
$32.1M
Subproject 5U54GM074946 · NIGMS · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI TERWILLIGER, THOMAS C. · 2005 to 2009
$20.2M
Chaperone Assisted CrystallographyR01GM072688 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2005 to 2012
$2.7M
High-performance affinity reagents for peptide epitopesR21CA132700 · NCI · UNIVERSITY OF CHICAGO · PI KOIDE, SHOHEI · 2008 to 2009
$367k
NCI NIH HHS R21 CA132700NCI NIH HHS R21-CA132700NIGMS NIH HHS 5T32GM07281-33NIGMS NIH HHS R01 GM072688NIGMS NIH HHS R01-GM72688NIGMS NIH HHS T32 GM007281NIGMS NIH HHS U54 GM074946NIGMS NIH HHS U54-GM74946
6 · The paper itself

Abstract

Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody mimic (or 'monobody'), termed HA4, that bound to the Abelson (Abl) kinase SH2 domain with low nanomolar affinity. SH2 protein microarray analysis and MS of intracellular HA4 interactors showed HA4's specificity, and a crystal structure revealed how this specificity is achieved. HA4 disrupted intramolecular interactions of Abl involving the SH2 domain and potently activated the kinase in vitro. Within cells, HA4 inhibited processive phosphorylation activity of Abl and also inhibited STAT5 activation. This work provides a design guideline for highly specific and potent inhibitors of a protein interaction domain and shows their utility in mechanistic and cellular investigations.

Indexed as

src Homology DomainsAmino Acid SequenceAntibodies, MonoclonalModels, MolecularMolecular Sequence DataOncogene Proteins v-ablPhosphorylationSequence Homology, Amino AcidAntibodies, MonoclonalOncogene Proteins v-abl

Identifiers

PMID20357770
PMCPMC2926940
OpenAlexW2089180620

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.