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Ubiquinone biosynthesis O-methyltransferase, mitochondrial precursor (3-demethylubiquinol 3-O-methyltransferase) (EC (Polyprenyldihydroxybenzoate methyltransferase) (EC [UG0215E05]


Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis.

The COQ3 gene in Saccharomyces cerevisiae encodes an O-methyltransferase required for two steps in the biosynthetic pathway of ubiquinone (coenzyme Q, or Q). This enzyme methylates an early Q intermediate, 3,4-dihydroxy-5-polyprenylbenzoic acid, as well as the final intermediate in the pathway, converting demethyl-Q to Q. This enzyme is also capable of methylating the distinct prokaryotic early intermediate 2-hydroxy-6-polyprenyl phenol. A full-length cDNA encoding the human homologue of COQ3 was isolated from a human heart cDNA library by sequence homology to rat Coq3. The clone contained a 933-base pair open reading frame that encoded a polypeptide with a great deal of sequence identity to a variety of eukaryotic and prokaryotic Coq3 homologues. In the region between amino acids 89 and 255 in the human sequence, the rat and human homologues are 87% identical, whereas human and yeast are 35% identical. When expressed in multicopy, the human construct rescued the growth of a yeast coq3 null mutant on a nonfermentable carbon source and restored coenzyme Q biosynthesis, although at lower levels than that of wild type yeast. In vitro methyltransferase assays using farnesylated analogues of intermediates in the coenzyme Q biosynthetic pathway as substrates showed that the human enzyme is active with all three substrates tested.

MeSH Terms

  • Aging
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Catechol O-Methyltransferase
  • Chromatography, High Pressure Liquid
  • DNA, Complementary
  • Gene Library
  • Humans
  • Methyltransferases
  • Models, Chemical
  • Molecular Sequence Data
  • Mutation
  • Myocardium
  • Rats
  • Saccharomyces cerevisiae
  • Sequence Homology, Amino Acid
  • Time Factors
  • Ubiquinone