Evidence map›Paper›PMID 29224332›Full record

ArticleBiochemistry2018

Statistical Coupling Analysis-Guided Library Design for the Discovery of Mutant Luciferases.

Mira D Liu, Elliot A Warner, Charlotte E Morrissey, Caitlyn W Fick, Taia S Wu, Marya Y Ornelas, Gabriela V Ochoa, Brendan S Zhang, Colin M Rathbun, William B Porterfield and 2 more

Abstract readComparative Study
In one paragraph

Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Multicomponent Bioluminescence Imaging with a π-Extended Luciferin.Journal of the American Chemical Society · 2020
    Article
  7. Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020
    Review
  8. Caged luciferins for bioluminescent activity-based sensing.Current opinion in biotechnology · 2019
    Review
  9. Review
  10. Review
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

12 authors.

Mira D LiuW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Elliot A WarnerW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Charlotte E MorrisseyW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Caitlyn W FickW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Taia S WuW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Marya Y OrnelasW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Gabriela V OchoaW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.
Brendan S Zhang
Colin M Rathbun
William B Porterfield
Jennifer A PrescherORCID 0000-0002-9250-4702
Aaron M LeconteW. M. Keck Science Department, Claremont McKenna, Pitzer, and Scripps Colleges , Claremont, California 91711, United States.ORCID 0000-0002-5789-9147

Funding

purchase of an All-in-One Fluorescence MicroscopeR01GM107630 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PRESCHER, JENNIFER · 2013 to 2021
$2.6M
NIGMS NIH HHS R01 GM107630
6 · The paper itself

Abstract

Directed evolution has proven to be an invaluable tool for protein engineering; however, there is still a need for developing new approaches to continue to improve the efficiency and efficacy of these methods. Here, we demonstrate a new method for library design that applies a previously developed bioinformatic method, Statistical Coupling Analysis (SCA). SCA uses homologous enzymes to identify amino acid positions that are mutable and functionally important and engage in synergistic interactions between amino acids. We use SCA to guide a library of the protein luciferase and demonstrate that, in a single round of selection, we can identify luciferase mutants with several valuable properties. Specifically, we identify luciferase mutants that possess both red-shifted emission spectra and improved stability relative to those of the wild-type enzyme. We also identify luciferase mutants that possess a >50-fold change in specificity for modified luciferins. To understand the mutational origin of these improved mutants, we demonstrate the role of mutations at N229, S239, and G246 in altered function. These studies show that SCA can be used to guide library design and rapidly identify synergistic amino acid mutations from a small library.

Indexed as

Gene LibraryGenes, InsectMutationAmino AcidsAmino Acid SequenceAmino Acid SubstitutionAnimalsComputational BiologyDrug DesignDrug DiscoveryFirefliesLuciferases, FireflyModels, MolecularProtein ConformationProtein StabilitySequence AlignmentAmino Acidsluciferase, PhotinusLuciferases, Firefly

Identifiers

PMID29224332
PMCPMC6192264

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.