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Photo Lynn Kamerlin

Lynn Kamerlin

Professor

Photo Lynn Kamerlin

Evolution of chalcone isomerase from a noncatalytic ancestor

Author

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

Summary, in English

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.

Publishing year

2018-06

Language

English

Pages

548-555

Publication/Series

Nature Chemical Biology

Volume

14

Issue

6

Document type

Journal article

Publisher

Nature Publishing Group

Keywords

  • Catalysis
  • Catalytic Domain
  • Chalcones/genetics
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Epistasis, Genetic
  • Escherichia coli
  • Evolution, Molecular
  • Fatty Acid-Binding Proteins/chemistry
  • Flavonoids/chemistry
  • Genes, Plant
  • Intramolecular Lyases/genetics
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Mutation
  • Phylogeny
  • Plant Proteins/metabolism
  • Plants/metabolism
  • Protein Conformation

Status

Published

ISBN/ISSN/Other

  • ISSN: 1552-4469