Evidence map›Paper›PMID 33432237›Full record

ArticleNature chemical biology2021

Laboratory evolution of a sortase enzyme that modifies amyloid-β protein.

Christopher J Podracky, Chihui An, Alexandra DeSousa, Brent M Dorr, Dominic M Walsh, David R Liu

Open access · bronzeAbstract read
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.1field-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

31 citing papers in PubMed, 63 citations in OpenAlex.

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  6. Amino acid variants at the P94 position inbioRxiv : the preprint server for biology · 2026
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  8. A Putative Interaction between the Transmembrane Domains ofThe journal of physical chemistry. B · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Christopher J PodrackyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Chihui AnDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Alexandra DeSousaLaboratory for Neurodegenerative Research, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Brent M DorrDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Dominic M WalshLaboratory for Neurodegenerative Research, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0718-6261
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID http://orcid.org/0000-0002-9943-7557
Brigham and Women's Hospital · USBroad Institute · USHarvard University · US

Funding

Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
Water-soluble Abeta and its role in Alzheimer's diseaseR01AG046275 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SELKOE, DENNIS J · 2014 to 2018
$1.8M
Howard Hughes Medical InstituteNIA NIH HHS R01 AG046275NIBIB NIH HHS R01 EB022376NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

Epitope-specific enzymes are powerful tools for site-specific protein modification but generally require genetic manipulation of the target protein. Here, we describe the laboratory evolution of the bacterial transpeptidase sortase A to recognize the LMVGG sequence in endogenous amyloid-β (Aβ) protein. Using a yeast display selection for covalent bond formation, we evolved a sortase variant that prefers LMVGG substrates from a starting enzyme that prefers LPESG substrates, resulting in a >1,400-fold change in substrate preference. We used this evolved sortase to label endogenous Aβ in human cerebrospinal fluid, enabling the detection of Aβ with sensitivities rivaling those of commercial assays. The evolved sortase can conjugate a hydrophilic peptide to Aβ

Indexed as

Amino Acid SequenceAminoacyltransferasesAmyloid beta-PeptidesBacterial ProteinsBinding SitesCysteine EndopeptidasesDirected Molecular EvolutionEscherichia coliHumansPeptide FragmentsProtein AggregatesProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsSaccharomyces cerevisiaeAminoacyltransferasesAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Bacterial ProteinsCysteine EndopeptidasesPeptide FragmentsProtein Aggregatessortase A

Identifiers

PMID33432237
PMCPMC7904614
OpenAlexW3118993376

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.