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A rotary mechanism for allostery in bacterial hybrid malic enzymes.

Harding CJ, Cadby IT, Moynihan PJ, Lovering AL
Nat Commun 12 1228 (2021)
Related entries: 6zn4, 6zn7, 6zn9, 6zne, 6zng, 6znk, 6znr, 6znt, 6znu

Cited: 3 times
EuropePMC logo PMID: 33623032

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.

Articles citing this publication (3)

  1. Bdellovibrio bacteriovorus phosphoglucose isomerase structures reveal novel rigidity in the active site of a selected subset of enzymes upon substrate binding. Meek RW, Cadby IT, Lovering AL. Open Biol 11 210098 (2021)
  2. Biophysical and biochemical studies support TP0094 as a phosphotransacetylase in an acetogenic energy-conservation pathway in Treponema pallidum. Brautigam CA, Deka RK, Tso SC, Liu WZ, Norgard MV. PLoS One 18 e0283952 (2023)
  3. Logistic Regression-Guided Identification of Cofactor Specificity-Contributing Residues in Enzyme with Sequence Datasets Partitioned by Catalytic Properties. Sugiki S, Niide T, Toya Y, Shimizu H. ACS Synth Biol 11 3973-3985 (2022)


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