Evidence map›Paper›PMID 29686356›Full record

ArticleNature chemical biology2018

Evolution of chalcone isomerase from a noncatalytic ancestor.

Miriam Kaltenbach, Jason R Burke, Mirco Dindo, Anna Pabis, Fabian S Munsberg, Avigayel Rabin, Shina C L Kamerlin, Joseph P Noel, Dan S Tawfik

Erratum issuedOpen access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

74 citing papers in PubMed, 149 citations in OpenAlex.

  1. Advances and opportunities for computational interrogation of plant proteins.The Plant journal : for cell and molecular biology · 2026
    Review
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  5. Favorable epistasis in ancestral diterpene synthases promoted convergent evolution of a resin acid precursor in conifers.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Identification of chalcone isomerase gene family inFrontiers in plant science · 2025
    Article
  10. Review
  11. Article
  12. Applications of ancestral sequence reconstruction for understanding the evolution of plant specialized metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  13. Evolution of plant metabolism: the state-of-the-art.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
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  20. Article

14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 4 countries.

Miriam KaltenbachDepartment of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Jason R BurkeHoward Hughes Medical Institute, Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Mirco DindoDepartment of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Anna PabisUppsala Biomedicinsk Centrum, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Fabian S MunsbergUppsala Biomedicinsk Centrum, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Avigayel RabinDepartment of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Shina C L KamerlinUppsala Biomedicinsk Centrum, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-3190-1173
Joseph P NoelHoward Hughes Medical Institute, Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, CA, USA. noel@salk.edu.ORCID http://orcid.org/0000-0002-1277-0331
Dan S TawfikDepartment of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. dan.tawfik@weizmann.ac.il.
Uppsala University · SESalk Institute for Biological Studies · USWeizmann Institute of Science · ILHebrew University of Jerusalem · ILUniversity of Verona · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable. Despite strong epistasis in other cases of protein evolution, CHI's laboratory reconstructed mutational trajectory shows weak epistasis. Thus, enantioselective CHI activity could readily emerge despite a catalytically inactive starting point. Accordingly, X-ray crystallography, NMR, and molecular dynamics simulations reveal reshaping of the active site toward a productive substrate-binding mode and repositioning of the catalytic arginine that was inherited from the ancestral fatty-acid binding proteins.

Indexed as

Evolution, MolecularCatalysisCatalytic DomainChalconesCloning, MolecularCrystallography, X-RayEpistasis, GeneticEscherichia coliFatty Acid-Binding ProteinsFlavonoidsGenes, PlantIntramolecular LyasesKineticsMagnetic Resonance SpectroscopyModels, MolecularMolecular Dynamics Simulationchalcone isomeraseChalconesFatty Acid-Binding ProteinsFlavonoidsIntramolecular Lyasesnaringenin chalconePlant Proteins

Identifiers

PMID29686356
OpenAlexW2743269523

What OpenQuestion holds

Textmetadata
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.