Structure of a membrane-embedded prenyltransferase homologous to UBIAD1

PLoS Biol. 2014 Jul 22;12(7):e1001911. doi: 10.1371/journal.pbio.1001911. eCollection 2014 Jul.


Membrane-embedded prenyltransferases from the UbiA family catalyze the Mg2+-dependent transfer of a hydrophobic polyprenyl chain onto a variety of acceptor molecules and are involved in the synthesis of molecules that mediate electron transport, including Vitamin K and Coenzyme Q. In humans, missense mutations to the protein UbiA prenyltransferase domain-containing 1 (UBIAD1) are responsible for Schnyder crystalline corneal dystrophy, which is a genetic disease that causes blindness. Mechanistic understanding of this family of enzymes has been hampered by a lack of three-dimensional structures. We have solved structures of a UBIAD1 homolog from Archaeoglobus fulgidus, AfUbiA, in an unliganded form and bound to Mg2+ and two different isoprenyl diphosphates. Functional assays on MenA, a UbiA family member from E. coli, verified the importance of residues involved in Mg2+ and substrate binding. The structural and functional studies led us to propose a mechanism for the prenyl transfer reaction. Disease-causing mutations in UBIAD1 are clustered around the active site in AfUbiA, suggesting the mechanism of catalysis is conserved between the two homologs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Archaeoglobus fulgidus / enzymology
  • Catalytic Domain
  • Cell Membrane / enzymology
  • Crystallography, X-Ray
  • Dimethylallyltranstransferase / chemistry*
  • Dimethylallyltranstransferase / genetics
  • Humans
  • Magnesium / chemistry
  • Models, Molecular
  • Protein Binding
  • Sequence Homology, Amino Acid


  • 4-hydroxybenzoic acid oligoprenyltransferase, E coli
  • Dimethylallyltranstransferase
  • UBIAD1 protein, human
  • Magnesium

Associated data

  • PDB/4TQ3
  • PDB/4TQ4
  • PDB/4TQ5
  • PDB/4TQ6