A rotary mechanism for allostery in bacterial hybrid malic enzymes

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Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of
malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux.
Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA,
a molecular indicator of the metabolic state of the cell. Here we solve the structure of a
MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA)
domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic
enzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scale
rearrangement that rotates the catalytic subunits 70° between the two states, identifying
MaeB as a new model enzyme for the study of ligand-induced conformational change. Our
work provides the mechanistic basis for metabolic control of hybrid malic enzymes, and
identifies inhibition-insensitive variants that may find utility in synthetic biology.
Original languageEnglish
Article number1228
JournalNature Communications
Issue number1
Publication statusPublished - 23 Feb 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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