Protein prenylation: enzymes, therapeutics, and biotechnology applications

ACS Chem Biol. 2015 Jan 16;10(1):51-62. doi: 10.1021/cb500791f. Epub 2014 Dec 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biotechnology / methods*
  • Dimethylallyltranstransferase / antagonists & inhibitors*
  • Dimethylallyltranstransferase / chemistry
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Protein Prenylation / drug effects*
  • Substrate Specificity
  • Terpenes / chemistry
  • Terpenes / pharmacology
  • Terpenes / therapeutic use*
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / chemistry

Substances

  • Enzyme Inhibitors
  • Terpenes
  • Dimethylallyltranstransferase
  • ras Proteins