cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases

J Biol Chem. 2016 Aug 26;291(35):18582-90. doi: 10.1074/jbc.R116.739490. Epub 2016 Jul 11.

Abstract

cis-Prenyltransferases (cis-PTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. cis-PTs catalyze consecutive condensation reactions of allylic diphosphate acceptor with isopentenyl diphosphate (IPP) in the cis (Z) configuration to generate linear polyprenyl diphosphate. The chain lengths of isoprenoid carbon skeletons vary widely from neryl pyrophosphate (C10) to natural rubber (C>10,000). The homo-dimeric bacterial enzyme, undecaprenyl diphosphate synthase (UPPS), has been structurally and mechanistically characterized in great detail and serves as a model for understanding the mode of action of eukaryotic cis-PTs. However, recent experiments have revealed that mammals, fungal, and long-chain plant cis-PTs are heteromeric enzymes composed of two distantly related subunits. In this review, the classification, function, and evolution of cis-PTs will be discussed with a special emphasis on the role of the newly described NgBR/Nus1 subunit and its plants' orthologs as essential, structural components of the cis-PTs activity.

Keywords: DHDDS; NUS1; NgBR; RER2; cis-prenyltransferase; dolichol; enzyme; genetic disease; glycosylation; glycosylphosphatidylinositol (GPI anchor); hCIT; lipid; polyprenol; polyprenol synthesis.

Publication types

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

MeSH terms

  • Animals
  • Dimethylallyltranstransferase* / genetics
  • Dimethylallyltranstransferase* / metabolism
  • Hemiterpenes* / genetics
  • Hemiterpenes* / metabolism
  • Humans
  • Organophosphorus Compounds* / metabolism
  • Plant Proteins* / metabolism
  • Protein Biosynthesis*
  • Rubber / metabolism*

Substances

  • Hemiterpenes
  • Organophosphorus Compounds
  • Plant Proteins
  • isopentenyl pyrophosphate
  • Rubber
  • Dimethylallyltranstransferase