Evidence map›Paper›PMID 30216041›Full record

ArticleACS chemical biology2018

Systematic Evaluation of Soluble Protein Expression Using a Fluorescent Unnatural Amino Acid Reveals No Reliable Predictors of Tolerability.

Zachary M Hostetler, John J Ferrie, Marc R Bornstein, Itthipol Sungwienwong, E James Petersson, Rahul M Kohli

Abstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Bioorthogonal Chemistry in Cellular Organelles.Topics in current chemistry (Cham) · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Synthesis and characterization of fluorescent amino acid dimethylaminoacridonylalanine.ARKIVOC : free online journal of organic chemistry · 2021
    Article
  18. Article
  19. Article
  20. A Genetically Encoded Diazirine Analogue for RNA-Protein Photo-crosslinking.Chembiochem : a European journal of chemical biology · 2020
    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

6 authors at 1 institution in 1 country.

Zachary M HostetlerDepartment of Medicine, Department of Biochemistry and Biophysics , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.ORCID 0000-0002-2830-8870
John J FerrieDepartment of Chemistry , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.ORCID 0000-0001-7934-7266
Marc R BornsteinDepartment of Medicine, Department of Biochemistry and Biophysics , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
Itthipol SungwienwongDepartment of Chemistry , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.
E James PeterssonDepartment of Chemistry , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.ORCID 0000-0003-3854-9210
Rahul M KohliDepartment of Medicine, Department of Biochemistry and Biophysics , University of Pennsylvania , Philadelphia , Pennsylvania 19104 , United States.ORCID 0000-0002-7689-5678
University of Pennsylvania · US

Funding

Predoctoral Training at the Chemistry-Biology InterfaceT32GM071339 · NIGMS · WISTAR INSTITUTE · PI MARMORSTEIN, RONEN, SPEICHER, DAVID W. · 2005 to 2019
$3.2M
Predoctoral Training at the Chemistry-Biology InterfaceT32GM133398 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Ronen Marmorstein, Ernest James Petersson · 2020 to 2026
$2.4M
The Molecular Basis for the Bacterial SOS SignalR01GM127593 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU, PETERSSON, ERNEST JAMES · 2018 to 2021
$1.2M
Protocol Driven Hemodynamic Support in Septic ShockK23GM071399 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI SEVRANSKY, JONATHAN E · 2005 to 2009
$671k
NIGMS NIH HHS K23 GM071399NIGMS NIH HHS R01 GM127593NIGMS NIH HHS T32 GM071339NIGMS NIH HHS T32 GM133398
6 · The paper itself

Abstract

Improvements in genetic code expansion have made preparing proteins with diverse functional groups almost routine. Nonetheless, unnatural amino acids (Uaas) pose theoretical burdens on protein solubility, and determinants of position-specific tolerability to Uaas remain underexplored. To broadly examine associations, we systematically assessed the effect of substituting the fluorescent Uaa, acridonylalanine, at more than 50 chemically, evolutionarily, and structurally diverse residues in two bacterial proteins: LexA and RecA. Surprisingly, properties that ostensibly contribute to Uaa tolerability-such as conservation, hydrophobicity, or accessibility-demonstrated no consistent correlations with resulting protein solubility. Instead, solubility is closely dependent on the location of the substitution within the overall tertiary structure, suggesting that intrinsic properties of protein domains, and not individual positions, are stronger determinants of Uaa tolerability. Consequently, those who seek to install Uaas in new target proteins should consider broadening, rather than narrowing, the types of residues screened for Uaa incorporation.

Indexed as

AcridonesAlanineBacterial ProteinsEscherichia coliEscherichia coli ProteinsFluorescent DyesLexA Repressor ProteinMutagenesisProtein EngineeringSerine EndopeptidasesSolubilityAcridonesAlanineBacterial ProteinsEscherichia coli ProteinsFluorescent DyesLexA Repressor ProteinSerine Endopeptidases

Identifiers

PMID30216041
PMCPMC6195468
OpenAlexW2891494391

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.