A rotary mechanism for allostery in bacterial hybrid malic enzymes

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A rotary mechanism for allostery in bacterial hybrid malic enzymes. / Harding, Christopher; Cadby, Ian; Moynihan, Patrick; Lovering, Andrew.

In: Nature Communications, Vol. 12, No. 1, 1228, 23.02.2021.

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@article{dc9a3cf307cd4683ab833b490b13ed6d,
title = "A rotary mechanism for allostery in bacterial hybrid malic enzymes",
abstract = "Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation ofmalate 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 aMaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA)domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malicenzyme active site, 60 {\AA} away. We demonstrate that allostery is governed by a large-scalerearrangement that rotates the catalytic subunits 70° between the two states, identifyingMaeB as a new model enzyme for the study of ligand-induced conformational change. Ourwork provides the mechanistic basis for metabolic control of hybrid malic enzymes, andidentifies inhibition-insensitive variants that may find utility in synthetic biology.",
author = "Christopher Harding and Ian Cadby and Patrick Moynihan and Andrew Lovering",
year = "2021",
month = feb,
day = "23",
doi = "10.1038/s41467-021-21528-2",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - A rotary mechanism for allostery in bacterial hybrid malic enzymes

AU - Harding, Christopher

AU - Cadby, Ian

AU - Moynihan, Patrick

AU - Lovering, Andrew

PY - 2021/2/23

Y1 - 2021/2/23

N2 - Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation ofmalate 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 aMaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA)domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malicenzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scalerearrangement that rotates the catalytic subunits 70° between the two states, identifyingMaeB as a new model enzyme for the study of ligand-induced conformational change. Ourwork provides the mechanistic basis for metabolic control of hybrid malic enzymes, andidentifies inhibition-insensitive variants that may find utility in synthetic biology.

AB - Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation ofmalate 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 aMaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA)domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malicenzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scalerearrangement that rotates the catalytic subunits 70° between the two states, identifyingMaeB as a new model enzyme for the study of ligand-induced conformational change. Ourwork provides the mechanistic basis for metabolic control of hybrid malic enzymes, andidentifies inhibition-insensitive variants that may find utility in synthetic biology.

U2 - 10.1038/s41467-021-21528-2

DO - 10.1038/s41467-021-21528-2

M3 - Article

C2 - 33623032

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1228

ER -