A rotary mechanism for allostery in bacterial hybrid malic enzymes

Christopher John Harding (), Ian Thomas Cadby, Patrick Joseph Moynihan and Andrew Lee Lovering ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21528-2

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DOI: 10.1038/s41467-021-21528-2

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