A rotary mechanism for allostery in bacterial hybrid malic enzymes
Date
23/02/2021Metadata
Show full item recordAbstract
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.
Citation
Harding , C J , Cadby , I T , Moynihan , P J & Lovering , A L 2021 , ' A rotary mechanism for allostery in bacterial hybrid malic enzymes ' , Nature Communications , vol. 12 , 1228 . https://doi.org/10.1038/s41467-021-21528-2
Publication
Nature Communications
Status
Peer reviewed
ISSN
2041-1723Type
Journal article
Description
This project was funded by BBSRC studentship 1500753 to C.J.H. and a BBSRC David Phillips fellowship to P.J.M. (BB/S010122/1).Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.