Evidence map›Paper›PMID 21171606›Full record

ArticleJournal of the American Chemical Society2011

Metal-substituted protein MRI contrast agents engineered for enhanced relaxivity and ligand sensitivity.

Victor S Lelyveld, Eric Brustad, Frances H Arnold, Alan Jasanoff

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Directed evolution ofChemical science · 2024
    Article
  6. Biogenic Imaging Contrast Agents.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  7. Review
  8. Article
  9. Directed Evolution of Artificial Metalloenzymes in Whole Cells.Angewandte Chemie (International ed. in English) · 2022
    Article
  10. Assembly and Evolution of Artificial Metalloenzymes withinJournal of the American Chemical Society · 2022
    Article
  11. Article
  12. De novo biosynthesis of a nonnatural cobalt porphyrin cofactor inProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Article
  14. Article
  15. Article
  16. Insulin Hexamer-Caged Gadolinium Ion as MRI Contrast-o-phore.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018
    Article
  17. Orthogonal Expression of an Artificial Metalloenzyme for Abiotic Catalysis.Chembiochem : a European journal of chemical biology · 2017
    Article
  18. Biomolecular MRI reporters: Evolution of new mechanisms.Progress in nuclear magnetic resonance spectroscopy · 2017
    Review
  19. Article
  20. 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

4 authors.

Victor S LelyveldDepartment of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Eric Brustad
Frances H Arnold
Alan Jasanoff

Funding

MRI probes for functional imaging of plasticity signals in the brainR01DA028299 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JASANOFF, ALAN · 2009 to 2013
$2.7M
Evolution of cytochrome p450s for the diversification of drug scaffoldsF32GM087102 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI BRUSTAD, ERIC MICHAEL · 2009 to 2011
$118k
NIDA NIH HHS R01 DA028299NIDA NIH HHS R01-DA28299NIGMS NIH HHS F32 GM087102NIGMS NIH HHS F32-GM087102
6 · The paper itself

Abstract

Engineered metalloproteins constitute a flexible new class of analyte-sensitive molecular imaging agents detectable by magnetic resonance imaging (MRI), but their contrast effects are generally weaker than synthetic agents. To augment the proton relaxivity of agents derived from the heme domain of cytochrome P450 BM3 (BM3h), we formed manganese(III)-containing proteins that have higher electron spin than their native ferric iron counterparts. Metal substitution was achieved by coexpressing BM3h variants with the bacterial heme transporter ChuA in Escherichia coli and supplementing the growth medium with Mn3+-protoporphyrin IX. Manganic BM3h variants exhibited up to 2.6-fold higher T1 relaxivities relative to native BM3h at 4.7 T. Application of ChuA-mediated porphyrin substitution to a collection of thermostable chimeric P450 domains resulted in a stable, high-relaxivity BM3h derivative displaying a 63% relaxivity change upon binding of arachidonic acid, a natural ligand for the P450 enzyme and an important component of biological signaling pathways. This work demonstrates that protein-based MRI sensors with robust ligand sensitivity may be created with ease by including metal substitution among the toolkit of methods available to the protein engineer.

Indexed as

Magnetic Resonance ImagingBacillus megateriumContrast MediaCytochrome P-450 Enzyme SystemLigandsManganeseProtein EngineeringProtein Structure, TertiaryProtoporphyrinsContrast MediaCytochrome P-450 Enzyme SystemLigandsManganeseprotoporphyrin IXProtoporphyrins

Identifiers

PMID21171606
PMCPMC3154012

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.