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Prenyl
Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar to lipid anchors like the GPI anchor, though direct evidence of this has not been observed. Prenyl groups (also called isoprenyl groups, having one hydrogen atom more than isoprene) have been shown to be important for protein–protein binding through specialized prenyl-binding domains. Protein prenylation Protein prenylation involves the transfer of either a farnesyl or a geranylgeranyl moiety to C-terminal cysteine(s) of the target protein. There are three enzymes that carry out prenylation in the cell, farnesyl transferase, Caax protease and geranylgeranyl transferase I. Farnesylation is a type of prenylation, a post-translational modification of proteins by which an isoprenyl group is added to a cysteine residue. It is an important ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prenyl Group
Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar to lipid anchored protein, lipid anchors like the GPI anchor, though direct evidence of this has not been observed. Prenyl groups (also called isoprenyl groups, having one hydrogen atom more than isoprene) have been shown to be important for protein–protein binding through specialized prenyl-binding domains. Protein prenylation Protein prenylation involves the transfer of either a farnesyl or a geranylgeranylation, geranylgeranyl moiety to C-terminal cysteine(s) of the target protein. There are three enzymes that carry out prenylation in the cell, farnesyl transferase, Caax protease and geranylgeranyl transferase I. Farnesylation is a type of prenylation, a post-translational modification of proteins by which an isoprenyl group is added ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lipid Anchored Protein
Lipid-anchored proteins (also known as lipid-linked proteins) are proteins located on the surface of the cell membrane that are covalently attached to lipids embedded within the cell membrane. These proteins insert and assume a place in the bilayer structure of the membrane alongside the similar fatty acid tails. The lipid-anchored protein can be located on either side of the cell membrane. Thus, the lipid serves to anchor the protein to the cell membrane. They are a type of proteolipids. The lipid groups play a role in protein interaction and can contribute to the function of the protein to which it is attached. Furthermore, the lipid serves as a mediator of membrane associations or as a determinant for specific protein-protein interactions. For example, lipid groups can play an important role in increasing molecular hydrophobicity. This allows for the interaction of proteins with cellular membranes and protein domains. In a dynamic role, lipidation can sequester a protein away f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rab (G-protein)
The Rab family of proteins is a member of the Ras superfamily of small G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab proteins generally possess a GTPase fold, which consists of a six-stranded beta sheet which is flanked by five alpha helices. Rab GTPases regulate many steps of membrane trafficking, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface. Function Rab proteins are peripheral membrane proteins, anchored to a membrane via a lipid group covalently linked to an amino acid. Specifi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Geranylgeranyltransferase Type 1
Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three enzymes in the prenyltransferase group. In specific terms, Geranylgeranyltransferase (GGTase 1) adds a 20-carbon isoprenoid called a geranylgeranyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminal of a protein. Geranylgeranyltransferase inhibitors are being investigated as anti-cancer agents. Function Prenyltransferases, including geranylgeranyltransferase, posttranslationally modify proteins by adding an isoprenoid lipid called a prenyl group to the carboxyl terminus of the target protein. This process, called prenylation, causes prenylated proteins to become membrane-associated due to the hydrophobic nature of the prenyl group. Most prenylated proteins are involved in cellular signaling, wherein membrane association is critical for function. Structure Geranylgeranyltransferase contains two subunits, α and β that are encoded by the ''FNT ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Farnesyltransferase
Farnesyltransferase () is one of the three enzymes in the prenyltransferase group. Farnesyltransferase (FTase) adds a 15-carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminus of a protein. Farnesyltransferase's targets include members of the Ras superfamily of small GTP-binding proteins critical to cell cycle progression. For this reason, several FTase inhibitors are undergoing testing as anti-cancer agents. FTase inhibitors have shown efficacy as anti-parasitic agents, as well. FTase is also believed to play an important role in development of progeria and various forms of cancers. Farnesyltransferase catalyzes the chemical reaction :farnesyl diphosphate + protein-cysteine \rightleftharpoons S-farnesyl protein + diphosphate Thus, the two substrates of this enzyme are farnesyl diphosphate and protein-cysteine, whereas its two products are S-farnesyl protein and diphosphate. Overview Farnesyltrans ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Farnesyltransferase
Farnesyltransferase () is one of the three enzymes in the prenyltransferase group. Farnesyltransferase (FTase) adds a 15-carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminus of a protein. Farnesyltransferase's targets include members of the Ras superfamily of small GTP-binding proteins critical to cell cycle progression. For this reason, several FTase inhibitors are undergoing testing as anti-cancer agents. FTase inhibitors have shown efficacy as anti-parasitic agents, as well. FTase is also believed to play an important role in development of progeria and various forms of cancers. Farnesyltransferase catalyzes the chemical reaction :farnesyl diphosphate + protein-cysteine \rightleftharpoons S-farnesyl protein + diphosphate Thus, the two substrates of this enzyme are farnesyl diphosphate and protein-cysteine, whereas its two products are S-farnesyl protein and diphosphate. Overview Farnesyltrans ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Statins
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low-density lipoprotein (LDL) carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via the mechanisms described by the lipid hypothesis. Statins are effective in lowering LDL cholesterol and so are widely used for primary prevention in people at high risk of cardiovascular disease, as well as in secondary prevention for those who have developed cardiovascular disease. Side effects of statins include muscle pain, increased risk of diabetes mellitus, and abnormal blood levels of liver enzymes. Additionally, they have rare but severe adverse effects, particularly muscle damage. They inhibit the enzyme HMG-CoA reductase which plays a central role in the production of cholesterol. High cholester ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ras (protein)
Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours. When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The three Ras genes in humans (''HRAS'', ''KRAS'', an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rab Escort Protein
Rab escort protein 1 (REP1) also known as rab proteins geranylgeranyltransferase component A 1 is an enzyme that in humans is encoded by the ''CHM'' gene. Function This gene encodes component A of the RAB geranylgeranyl transferase holoenzyme. In the dimeric holoenzyme, this subunit binds unprenylated Rab GTPases and then presents them to the catalytic Rab GGTase subunit for the geranylgeranyl transfer reaction. Rab GTPases need to be on either one or two cysteine residues in their C-terminus to localize to the correct intracellular membrane. Interactions CHM (gene) has been shown to interact with RAB1A, RAB7A and RAB3A. Clinical significance Mutations in this gene are a cause of choroideremia; also known as tapetochoroidal dystrophy (TCD). This X-linked disease is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina. See also * Rab (G-protein) The Rab family of proteins is a member of the Ras superfamily of small G proteins. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bisphosphonates
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate () groups. They are thus also called diphosphonates ('' bis-'' or '' di-'' + ''phosphonate''). Evidence shows that they reduce the risk of fracture in post-menopausal women with osteoporosis. Bone tissue undergoes constant remodeling and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts destroying bone. Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss. The uses of bisphosphonates include the prevention and treatment of osteoporosis, Paget's disease of bone, bone metastasis (with or without hypercalcemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Farnesyl Pyrophosphate
Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport chain), as well as dehydrodolichol diphosphate (a precursor of dolichol, which transports proteins to the ER lumen for ''N''-glycosylation). Biosynthesis Farnesyl pyrophosphate synthase (a prenyl transferase) catalyzes sequential condensation reactions of dimethylallyl pyrophosphate with 2 units of 3-isopentenyl pyrophosphate to form farnesyl pyrophosphate, as is shown in the following two steps: * Dimethylallyl pyrophosphate reacts with 3-isopentenyl pyrophosphate to form geranyl pyrophosphate: * Geranyl pyrophosphate then reacts with another molecule of 3-isopentenyl pyrophosphate to form farnesyl pyrophosphate Pharmacology The above reactions are inhibited by bisphosphonates (used for osteoporosis). Farnesyl pyrophosphate is a sel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Farnesyltransferase Inhibitor
The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras (protein), which is commonly abnormally active in cancer. Background Studies have suggested that interference with certain post-translational modification processes seem to have quite a high selectivity for targeting cells displaying tumour phenotypes, although the reason for this is a matter of controversy. After translation, Ras goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-Ras protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-Ras (the implications of this are discussed below). Farnesyl is necessary to attach Ras ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
