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

Structure of a membrane-embedded prenyltransferase homologous to UBIAD1.

Author information

1
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
2
Department of Biology, Texas A&M University, College Station, Texas, United States of America.
3
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.

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.

PMID:
25051182
PMCID:
PMC4106721
DOI:
10.1371/journal.pbio.1001911
[Indexed for MEDLINE]
Free PMC Article
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