RRC ID 56355
Author Bernhardsgrütter I, Vögeli B, Wagner T, Peter DM, Cortina NS, Kahnt J, Bange G, Engilberge S, Girard E, Riobé F, Maury O, Shima S, Zarzycki J, Erb TJ.
Title The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite.
Journal Nat. Chem. Biol.
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.
Volume 14(12)
Pages 1127-1132
Published 2018-12
DOI 10.1038/s41589-018-0153-x
PII 10.1038/s41589-018-0153-x
PMID 30374166
PMC PMC6499725
MeSH Acyl Coenzyme A / metabolism* Catalysis Coenzyme A Ligases / chemistry* Coenzyme A Ligases / genetics Coenzyme A Ligases / metabolism* Crystallography, X-Ray Kinetics Protein Domains Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Scattering, Small Angle Sphingomonadaceae / enzymology Sphingomonadaceae / genetics X-Ray Diffraction
IF 12.154
Prokaryotes E. coli ASKA(-)