PMID: 8943151Nov 12, 1996Paper

Characterisation of protein isoprenylation in procyclic form Trypanosoma brucei

Molecular and Biochemical Parasitology
H FieldM C Field

Abstract

Protein modification by isoprenylation is essential in mammals and other eukaryotes, but has not been demonstrated in the parasitic protozoa of the order kinetoplastida. A key regulatory enzyme of the mevalonate pathway, hydroxymethylglutaryl-coenzyme A reductase (HMG-R), and end products of the path, including dolichols, are present in Trypanosoma brucei. By metabolical labelling of procyclic form trypanosomes in the presence of compactin, an efficient inhibitor of HMG-R, followed by one-dimensional gel electrophoresis, we demonstrate that protein isoprenylation indeed takes place in this organism and at least 14 polypeptides bear the modification. Further characterization of labelled isoprenyl groups by methyl iodide cleavage and high pressure liquid chromatography identified both the farnesyl and geranylgeranyl moieties found covalently attached to proteins in other eukaryotes. The latter moiety was more abundant, as found in mammalian systems. Prolonged incubation with compactin grossly affected cell morphology and altered a number of subcellular structures as seen by electron microscopy. High concentrations of compactin were toxic, whilst lower concentrations were cytostatic. The primary morphological lesion is distinct fr...Continue Reading

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Citations

Sep 25, 1998·Molecular and Biochemical Parasitology·D ChakrabartiC M Allen
Aug 26, 1999·Parasitology Today·M C FieldH Field
Sep 8, 1999·The Biochemical Journal·M P Hasne, F Lawrence
Nov 17, 2011·Antioxidants & Redox Signaling·Esther JortzikKatja Becker
Mar 2, 2011·Antimicrobial Agents and Chemotherapy·Fabiana Morandi JordãoAlejandro Miguel Katzin
Aug 15, 2001·Antimicrobial Agents and Chemotherapy·I C MouraE A Kimura
Sep 9, 2011·Memórias do Instituto Oswaldo Cruz·Fabiana Morandi JordãoAlejandro Miguel Katzin
Mar 1, 2013·MedChemComm·Joshua D Ochocki, Mark D Distefano
Aug 27, 2002·The Journal of Biological Chemistry·Debopam ChakrabartiCharles M Allen
May 22, 2001·The Journal of Biological Chemistry·J L Nepomuceno-SilvaU G Lopes
May 29, 1999·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M A Barcinski, G A DosReis
Sep 12, 2002·Expert Opinion on Therapeutic Targets·Karl A Werbovetz
May 4, 2017·Journal of Basic Microbiology·Abdul M BaigNaveed A Khan
Jan 9, 2004·Journal of Medicinal Chemistry·Junko OhkandaAndrew D Hamilton
Apr 13, 2010·Molecular and Biochemical Parasitology·Terry K Smith, Peter Bütikofer

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