Materials Thrombin (bovine plasma, 1880 NIH units/mg protein) was purchased from Sigma (St. Louis, MO, U.S.A.). Simvastatin, fluvastatin and pravastatin were supplied by Merck & Co. (Rahway, N.J., U.S.A.), Novartis Pharma Inc. (Tokyo, Japan) and Sankyo Co. (Tokyo, Japan), respectively. TFLLR-NH2 (PAR1-activating peptide) and GYPGKFNH2 (PAR4-activating peptide) were purchased from Bachem (Bubend...

Based on crystallographic data of the complexes 2-alkyl(amino)ethyl-1,1-bisphosphonates-Trypanosoma cruzi farnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated against T. cruzi, the responsible agent of Chagas disease and against Toxoplasma gondii, the etiologic agent of toxoplasmosis and al...

Farnesyl pyrophosphate synthase (FPPS) is an enzyme of the mevalonate pathway and a well-established therapeutic target. Recent research has focused around a newly identified druggable pocket near the enzyme's active site. Pharmacological exploitation of this pocket is deemed promising; however, its natural biological function, if any, is yet unknown. Here we report that the product of FPPS, fa...

All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli. The immune system activates when damaged or injured cells release damage-associated molecular patterns (DAMPs). In addition well-characterized DAMPs such as high-mobility group box 1 and adenosine triphosphate, studies on new classes emerged. Here, we review recent repor...

In the yeast Saccharomyces cerevisiae the RER2 and SRT1 genes encode Rer2 and Srt1 proteins with cis-prenyltransferase (cis-PT-ase) activity. Both cis-PT-ases utilize farnesyl diphosphate (FPP) as a starter for polyprenyl diphosphate (dolichol backbone) formation. The products of the Rer2 and Srt1 proteins consist of 14-17 and 18-23 isoprene units, respectively. In this work we demonstrate that...

Pectin administered to Uncaria tomentosa cell suspension cultures, was found to increase the production of triterpene acids (ursolic and oleanolic acid), however, neither growth nor sterol accumulation were affected. Cell cultures showed that pectin treatment caused a rapid threefold increase in the activities of enzymes involved in the biosynthesis of C(5) and C(30 )isoprenoid, such as isopent...

K-Ras4B is targeted to the plasma membrane by a farnesyl modification that operates in conjunction with a polybasic domain. We characterized a farnesyl-electrostatic switch whereby protein kinase C phosphorylates K-Ras4B on serine 181 in the polybasic region and thereby induces translocation from the plasma membrane to internal membranes that include the endoplasmic reticulum (ER) and outer mit...