Protein prenylation: enzymes, therapeutics, and biotechnology applications.
Protein prenylation is a ubiquitous covalent post-translational modification found in all eukaryotic cells, comprising attachment of either a farnesyl or a geranylgeranyl isoprenoid. It is essential for the proper cellular activity of numerous proteins, including Ras family GTPases and heterotrimeric G-proteins. Inhibition of prenylation has been extensively investigated to suppress the activity of oncogenic Ras proteins to achieve antitumor activity. Here, we review the biochemistry of the prenyltransferase enzymes and numerous isoprenoid analogs synthesized to investigate various aspects of prenylation and prenyltransferases. We also give an account of the current status of prenyltransferase inhibitors as potential therapeutics against several diseases including cancers, progeria, aging, parasitic diseases, and bacterial and viral infections. Finally, we discuss recent progress in utilizing protein prenylation for site-specific protein labeling for various biotechnology applications.
Department of Chemistry, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Charuta C
CC
Palsuledesai
Mark D
MD
Distefano
D000818:Animals; D001709:Biotechnology / Q000379:methods*; D004122:Dimethylallyltranstransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D017368:Protein Prenylation / Q000187:drug effects*; D013379:Substrate Specificity; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry
D004791:Enzyme Inhibitors; D013729:Terpenes; D004122:Dimethylallyltranstransferase; D018631:ras Proteins