title: cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases.
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.
authors.affiliation: From the Department of Pharmacology and Vascular Biology and Therapeutics Program (VBT), Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Kariona A
authors.initials: KA
authors.lastname: Grabińska
authors.affiliation: From the Department of Pharmacology and Vascular Biology and Therapeutics Program (VBT), Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Eon Joo
authors.initials: EJ
authors.lastname: Park
authors.affiliation: From the Department of Pharmacology and Vascular Biology and Therapeutics Program (VBT), Yale University School of Medicine, New Haven, Connecticut 06520 william.sessa@yale.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism; D045782:Hemiterpenes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009943:Organophosphorus Compounds / Q000378:metabolism; D010940:Plant Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D012408:Rubber / Q000378:metabolism*
chemical_list: D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D010940:Plant Proteins; C004809:isopentenyl pyrophosphate; D012408:Rubber; D004122:Dimethylallyltranstransferase
keywords: DHDDS; NUS1; NgBR; RER2; cis-prenyltransferase; dolichol; enzyme; genetic disease; glycosylation; glycosylphosphatidylinositol (GPI anchor); hCIT; lipid; polyprenol; polyprenol synthesis