نتایج جستجو برای: prenylation
تعداد نتایج: 805 فیلتر نتایج به سال:
The antimalarial agent fosmidomycin is a validated inhibitor of the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite, Plasmodium falciparum. Since multiple classes of prenyltransferase inhibitors kill P. falciparum, we hypothesized that protein prenylation was one of the essential functions of this pathway. We found that MEP pathway inhi...
Protein prenylation is the addition of a 15 or 20 carbon lipid to cysteine near carboxyl terminus target proteins. Prentlyation increases hydrophobicity, which facilitates membrane associations and protein-protein interaction. generally conserved among eukaryotes, mutations in genes that carry out are lethal animals yeast. In plants not always lethal, but they do affect development, disease res...
Accumulation of β-amyloid (Aβ) inside brain neurons is an early and crucial event in Alzheimer's disease (AD). Studies in brains of AD patients and mice models of AD suggested that cholesterol homeostasis is altered in neurons that accumulate Aβ. Here we directly investigated the role of intracellular oligomeric Aβ(42) (oAβ(42)) in neuronal cholesterol homeostasis. We report that oAβ(42) induce...
Rab geranylgeranyltransferase (RabGGTase or GGTase-II) catalyzes the post-translational prenylation of Rab proteins. Rab proteins are recognized as substrates only when they are complexed to Rab Escort Protein (REP). The classical model of prenylation complex assembly assumes initial formation of the Rab.REP binary complex, which subsequently binds to RabGGTase loaded with the isoprenoid donor ...
Farnesyl:protein transferase (FPTase) inhibitors were developed as anti-Ras drugs, but they fail to inhibit Ki-Ras activity because Ki-Ras can be modified by geranylgeranyl:protein transferase type-I (GGPTase-I). L-778,123, an inhibitor of FPTase and GGPTase-I, was developed in part because it can completely inhibit Ki-Ras prenylation. To support the clinical development of L-778,123, we develo...
Rab GTPases are post-translationally modified by addition of geranylgeranyl moieties to carboxyl-terminal cysteine residues. For Rab proteins ending with xxCC xCxC and CCxx motifs this modification is catalysed by geranylgeranyltransferase type II (GGTaseII), and is entirely dependent on the Rab substrate being bound to Rab escort protein (REP). Several Rab proteins contain carboxyl-terminal Ca...
Ras signaling is often dysregulated and plays essential roles for the maintenance of glioblastoma. The proper function of Ras depends largely on the appropriate post-translational modification termed prenylation. Targeting protein prenylation therefore represents an alternative therapeutic strategy in glioblastoma. In this study, we demonstrate that prenylation inhibition by atorvastatin is act...
Protein S-prenylation is a lipid modification that regulates membrane-protein and protein-protein interactions in cell signaling. Though sites of protein S-prenylation can be predicted based upon conserved C-terminal CaaX or CC/CXC motifs, biochemical detection of protein S-prenylation in cells is still challenging. Herein, we report an alkynyl-isoprenol chemical reporter (alk-FOH) as an effici...
Prenylation primarily by geranylgeranylation is required for membrane attachment and function of type I Rho of Plants (ROPs) and Gγ proteins, while type II ROPs are attached to the plasma membrane by S-acylation. Yet, it is not known how prenylation affects ROP membrane interaction dynamics and what are the functional redundancy and specificity of type I and type II ROPs. Here, we have used the...
C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids. Therefore, the selective installation prenyl group at position NH is great significance. However, known protocols generally require multi-step procedure and stoichiometric promoters. Herein we develop one-step prenylation indole with cheap tert-prenyl alcohol enabled by acid catalysis. Salient features include goo...
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