Structure of a Membrane-Embedded Prenyltransferase Homologous to UBIAD1

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. © 2014 huang et al.