Structural Insights into Ubiquinone Biosynthesis in Membranes

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Science  21 Feb 2014:
Vol. 343, Issue 6173, pp. 878-881
DOI: 10.1126/science.1246774

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Catalysis in the Membrane

Enzymes in the UbiA superfamily of integral membrane proteins synthesize lipid-soluble aromatics such as ubiquinones and chlorophylls that function in energy storage and energy transfer in mitochondrial and chloroplast membranes. Cheng and Li (p. 878) report structures of an archaeal UbiA protein in both apo and substrate-bound states. The structures show a large active site with a lateral portal that is likely to give access to the long-chain isoprenoid substrates. The findings suggest a mechanism for substrate recognition and catalysis and can explain disease-related mutants in eukaryotic homologs.


Biosynthesis of ubiquinones requires the intramembrane UbiA enzyme, an archetypal member of a superfamily of prenyltransferases that generates lipophilic aromatic compounds. Mutations in eukaryotic superfamily members have been linked to cardiovascular degeneration and Parkinson’s disease. To understand how quinones are produced within membranes, we report the crystal structures of an archaeal UbiA in its apo and substrate-bound states at 3.3 and 3.6 angstrom resolution, respectively. The structures reveal nine transmembrane helices and an extramembrane cap domain that surround a large central cavity containing the active site. To facilitate the catalysis inside membranes, UbiA has an unusual active site that opens laterally to the lipid bilayer. Our studies illuminate general mechanisms for substrate recognition and catalysis in the UbiA superfamily and rationalize disease-related mutations in humans.

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