title: Analogs of farnesyl diphosphate alter CaaX substrate specificity and reactions rates of protein farnesyltransferase.
abstract: Attempts to identify the prenyl-proteome of cells or changes in prenylation following drug treatment have used 'clickable' alkyne-modified analogs of the lipid substrates farnesyl- and geranylgeranyl-diphosphate (FPP and GGPP). We characterized the reactivity of four alkyne-containing analogs of FPP with purified protein farnesyltransferase and a small library of dansylated peptides using an in vitro continuous spectrofluorimetric assay. These analogs alter prenylation specificity and reactivity suggesting that in vivo results obtained using these FPP analogs should be interpreted cautiously.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Jennings
authors.affiliation: Department of Chemistry and Biochemistry, Mercyhurst University, Erie, PA 16546, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Danowitz
authors.affiliation: Department of Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Distefano
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: fierke@umich.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fierke
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D000480:Alkynes / Q000737:chemistry; D057930:Click Chemistry; D007700:Kinetics; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000378:metabolism*; D017368:Protein Prenylation; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000480:Alkynes; D010455:Peptides; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase
keywords: Click chemistry; Post-translational modification; Protein farnesylation; Protein prenylation; Substrate analogs