Evidence map›Paper›PMID 23023596›Full record

ArticleNature methods2012

Global identification of peptidase specificity by multiplex substrate profiling.

Anthony J O'Donoghue, A Alegra Eroy-Reveles, Giselle M Knudsen, Jessica Ingram, Min Zhou, Jacob B Statnekov, Alexander L Greninger, Daniel R Hostetter, Gang Qu, David A Maltby and 5 more

Open access · greenAbstract readValidation Study
In one paragraph

Article in Nature methods, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

107 citing papers in PubMed, 193 citations in OpenAlex.

  1. Article
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  13. Enhancing schistosomiasis drug discovery approaches with optimized proteasome substrates.Protein science : a publication of the Protein Society · 2025
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47 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

15 authors at 5 institutions in 1 country.

Anthony J O'DonoghueDepartment of Pharmaceutical Chemistry, University of California, San Francisco, USA.
A Alegra Eroy-Reveles
Giselle M Knudsen
Jessica Ingram
Min Zhou
Jacob B Statnekov
Alexander L Greninger
Daniel R Hostetter
Gang Qu
David A Maltby
Marc O Anderson
Joseph L Derisi
James H McKerrow
Alma L Burlingame
Charles S Craik
University of California, San Francisco · USCenter for Discovery · USHoward Hughes Medical Institute · USSan Francisco State University · USUniversity of Maryland, College Park · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
YEAST THREONINE &SERINE KINASESP41RR001614 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1985 to 2011
$24.1M
UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
Bio-Organic Biomedical Mass Spectromy ResourceP41GM103481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2012 to 2015
$6.4M
Allosteric Inhibition of a Family of Proteolytic EnzymesR01GM104659 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2013 to 2016
$1.2M
A Technological Platform for the Identification of Serine Proteases in CancerR01CA128765 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2009 to 2011
$1.1M
NCI NIH HHS R01 CA128765NCRR NIH HHS P41 RR001614NIGMS NIH HHS K12 GM081266NIGMS NIH HHS P41 GM103481NIGMS NIH HHS P50 GM082250NIGMS NIH HHS R01 GM104659NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

We developed a simple and rapid multiplex substrate-profiling method to reveal the substrate specificity of any endo- or exopeptidase using liquid chromatography-tandem mass spectrometry sequencing. We generated a physicochemically diverse library of peptides by incorporating all combinations of neighbor and near-neighbor amino acid pairs into decapeptide sequences that are flanked by unique dipeptides at each terminus. Addition of a panel of evolutionarily diverse peptidases to a mixture of these tetradecapeptides generated information on prime and nonprime sites as well as on substrate specificity that matched or expanded upon known substrate motifs. This method biochemically confirmed the activity of the klassevirus 3C protein responsible for polypeptide processing and allowed granzyme B substrates to be ranked by enzymatic turnover efficiency using label-free quantitation of precursor-ion abundance. Additionally, the proteolytic secretions from schistosome parasitic flatworm larvae and a pancreatic cancer cell line were deconvoluted in a subtractive strategy using class-specific peptidase inhibitors.

Indexed as

Substrate Specificity3C Viral ProteasesAnimalsCarboxypeptidasesCarcinoma, Pancreatic DuctalCathepsin ECell Line, TumorChromatography, LiquidCysteine EndopeptidasesExopeptidasesGranzymesHumansMicePancreatic ElastasePeptide HydrolasesPeptide Library3C Viral ProteasesCarboxypeptidasesCathepsin ECysteine EndopeptidasesExopeptidasesGranzymeslysosomal Pro-X carboxypeptidasePancreatic ElastasePeptide HydrolasesPeptide LibraryPeptidesViral Proteins

Identifiers

PMID23023596
PMCPMC3707110
OpenAlexW2165824222

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.