title: Structure of a membrane-embedded prenyltransferase homologous to UBIAD1.
abstract: 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.
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Hua
authors: H
authors: Huang
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Elena J
authors: EJ
authors: Levin
authors: Department of Biology, Texas A&M University, College Station, Texas, United States of America.
authors: Shian
authors: S
authors: Liu
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Yonghong
authors: Y
authors: Bai
authors: Department of Biology, Texas A&M University, College Station, Texas, United States of America; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, Texas, United States of America.
authors: Steve W
authors: SW
authors: Lockless
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Ming
authors: M
authors: Zhou
mesh_terms: D000595:Amino Acid Sequence; D019611:Archaeoglobus fulgidus / Q000201:enzymology; D020134:Catalytic Domain; D002462:Cell Membrane / Q000201:enzymology; D018360:Crystallography, X-Ray; D004122:Dimethylallyltranstransferase / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: C509554:4-hydroxybenzoic acid oligoprenyltransferase, E coli; D004122:Dimethylallyltranstransferase; C425464:UBIAD1 protein, human; D008274:Magnesium