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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.
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 language | English |
---|---|
Article number | 1228 |
Journal | Nature Communications |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 23 Feb 2021 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry,Genetics and Molecular Biology
- General Physics and Astronomy
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Dive into the research topics of 'A rotary mechanism for allostery in bacterial hybrid malic enzymes'. Together they form a unique fingerprint.Projects
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Peptidoglycan release and recycling in pathogenic mycobacteria
Moynihan, P. (Principal Investigator)
Biotechnology & Biological Sciences Research Council
1/04/19 → 31/03/25
Project: Research