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A rotary mechanism for allostery in bacterial hybrid malic enzymes

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  • Christopher John Harding

    (University of Birmingham)

  • Ian Thomas Cadby

    (University of Birmingham)

  • Patrick Joseph Moynihan

    (University of Birmingham)

  • Andrew Lee Lovering

    (University of Birmingham)

Abstract

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.

Suggested Citation

  • Christopher John Harding & Ian Thomas Cadby & Patrick Joseph Moynihan & Andrew Lee Lovering, 2021. "A rotary mechanism for allostery in bacterial hybrid malic enzymes," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21528-2
    DOI: 10.1038/s41467-021-21528-2
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