[18] Prenylcysteine analogs to study function of carboxylmethylation in signal transduction

Characterization of prenylated protein methyltransferase in Leishmania

“…PPMTase has been identified in various cells [1][2][3][4][5][6][7][8][9]. This enzyme catalyses the methylesterification of the α-carboxy group of prenylcysteine in native proteins as well as in synthetic Sfarnesylated and geranylgeranylated cysteine peptides and isoprenylated analogues of cysteine [1,7,10].…”

“…This enzyme catalyses the methylesterification of the α-carboxy group of prenylcysteine in native proteins as well as in synthetic Sfarnesylated and geranylgeranylated cysteine peptides and isoprenylated analogues of cysteine [1,7,10]. This post-translational modification is the last step in the processing of a group of proteins that are synthesized with a Cys-Xaa-Xaa-Xaa, CysXaa-Cys or Xaa-Cys-Cys C-terminal sequence [11,12].…”

“…It has been reported that carboxymethylation is involved in the activation of platelets, neutrophils and macrophages [1,7,11] as well as that of normal pancreatic rat islets [13,14] and a pancreatic β-cell line [8]. It is also implicated in the regulation of intracellular pH homeostasis [15].…”

“…It is also implicated in the regulation of intracellular pH homeostasis [15]. The inhibition of protein carboxymethyl- ation alters chemotactic responses [1,7] and insulin secretion [8,13]. Both heterotrimeric and small G-proteins have been implicated in these events [1,7].…”

“…The inhibition of protein carboxymethyl- ation alters chemotactic responses [1,7] and insulin secretion [8,13]. Both heterotrimeric and small G-proteins have been implicated in these events [1,7]. The aim of the present study was to characterize the prenylated protein methyltransferase activity in Leishmania and to compare its properties with that of the known mammalian enzyme, because differences between the leishmanial and mammalian enzymes could have therapeutic implications.…”