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Nat Chem Biol. 2018 Dec;14(12):1127-1132. doi: 10.1038/s41589-018-0153-x. Epub 2018 Oct 29.

The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite.

Author information

1
Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
2
Microbial Protein Structure Group, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
3
Proteomics Core Facility, Max-Planck-Institute for Terrestrial Microbiology, Marburg, Germany.
4
LOEWE Center for Synthetic Microbiology (Synmikro), Marburg, Germany.
5
Faculty of Chemistry, Philipps-University-Marburg, Marburg, Germany.
6
Institut de Biologie Structurale, University Grenoble Alpes, CEA, CNRS, Grenoble, France.
7
Laboratoire de Chimie, École Normale Supérieure de Lyon, Lyon, France.
8
Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany. toerb@mpi-marburg.mpg.de.

Abstract

Cells must cope with toxic or reactive intermediates formed during metabolism. One coping strategy is to sequester reactions that produce such intermediates within specialized compartments or tunnels connecting different active sites. Here, we show that propionyl-CoA synthase (PCS), an ∼ 400-kDa homodimer, three-domain fusion protein and the key enzyme of the 3-hydroxypropionate bi-cycle for CO2 fixation, sequesters its reactive intermediate acrylyl-CoA. Structural analysis showed that PCS forms a multicatalytic reaction chamber. Kinetic analysis suggested that access to the reaction chamber and catalysis are synchronized by interdomain communication. The reaction chamber of PCS features three active sites and has a volume of only 33 nm3. As one of the smallest multireaction chambers described in biology, PCS may inspire the engineering of a new class of dynamically regulated nanoreactors.

PMID:
30374166
PMCID:
PMC6499725
DOI:
10.1038/s41589-018-0153-x
[Indexed for MEDLINE]
Free PMC Article

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