Evidence map›Paper›PMID 39083370›Full record

ArticleJournal of the American Chemical Society2024

Kinetic Resolution of Epimeric Proteins Enables Stereoselective Chemical Mutagenesis.

Guljannat Ablat, Neev Lawton, Ruqaiya Alam, Bethany A Haynes, Sabrina Hossain, Thomas Hicks, Sasha L Evans, James A Jarvis, Timothy J Nott, Rivka L Isaacson and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

11 authors.

Guljannat AblatDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Neev LawtonDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Ruqaiya AlamDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Bethany A HaynesDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Sabrina HossainDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Thomas HicksDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
Sasha L EvansDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.ORCID 0000-0003-0669-3824
James A JarvisRandall Centre for Cell and Molecular Biophysics and Centre for Biomolecular Spectroscopy, King's College London, New Hunts House, London SE1 1UL, U.K.ORCID 0000-0001-8630-7617
Timothy J NottDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.ORCID 0000-0002-5210-4931
Rivka L IsaacsonDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.ORCID 0000-0002-9978-8904
Manuel M MüllerDepartment of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.ORCID 0000-0001-6701-0893

Funding

Wellcome Trust
6 · The paper itself

Abstract

Chemical mutagenesis via dehydroalanine (Dha) is a powerful method to tailor protein structure and function, allowing the site-specific installation of post-translational modifications and non-natural functional groups. Despite the impressive versatility of this method, applications have been limited, as products are formed as epimeric mixtures, whereby the modified amino acid is present as both the desired l-configuration and a roughly equal amount of the undesired d-isomer. Here, we describe a simple remedy for this issue: removal of the d-isomer via proteolysis using a d-stereoselective peptidase, alkaline d-peptidase (AD-P). We demonstrate that AD-P can selectively cleave the d-isomer of epimeric residues within histone H3, GFP, Ddx4, and SGTA, allowing the installation of non-natural amino acids with stereochemical control. Given the breadth of modifications that can be introduced via Dha and the simplicity of our method, we believe that stereoselective chemoenzymatic mutagenesis will find broad utility in protein engineering and chemical biology applications.

Indexed as

MutagenesisAlanineHistonesKineticsProtein EngineeringProteinsStereoisomerismAlaninedehydroalanineHistonesProteins

Identifiers

PMID39083370
PMCPMC11328163

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Registered trials

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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.