Translocation factor

Chromosomal mutations have also been described which produce a modified translocation factor protein with lowered affinity for fusidic acid. 

S0e, R., Mosley, R. T., Justice, M., Nielsen-Kahn, J., Shastry, M., and Merrill, A. R. Andersen, G. R. (2007). Sordarin derivatives induce a novel conformation of the yeast ribosome translocation factor eEF2. J. Biol. Chem. 282, 657—666. 

The final step in elongation is known as translocation (fig. 29.17). This reaction, like aminoacyl-tRNA binding, is catalyzed by a factor (the translocation factor, known as EF-G in prokaryotic systems and EF-2 in eukaryotic systems) that cycles on and off the ribosome and hydrolyzes GTP in the process. The overall purpose of translocation is to move the ribosome physically along the mRNA to expose the next codon for translation. 

Ramon G, Descombey P (1925) Sur 1 immunization antitetanique et sur la production de l antitoxine tetanique Compt Rend Soc Biol 93 508-98 Ratts R, Zeng H, Berg EA, Blue C, McComb ME et al. (2003) The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex. J Cell Biol 160 1139-50... 

The structurally related antibiotics kirromycin and pulvomycin both act upon EF-Tu of most bacteria (and chloroplasts) although not upon its eucaryal (EF-la) counterpart [158,159]. The steroid antibiotic fusidic acid interacts systematically with both the eucaryal (EF-2) and the bacterial (EF-G) translocating factors, including chloroplasts of higher plants. Diphtheria toxin (fragment A) discriminates between bacterial-mitochondrial and eucaryal translocating factors by selectively and irreversibly impairing the eucaryal EF-2 factors [160,161]. 

A further functionally diverse class is made up of the proteins involved in protein biosynthesis and membrane transport. GTPases with functions in protein biosynthesis include the elongation factors, termination factors and peptide translocation factors. These are mostly monomeric proteins with molecular weights of 40 - 50 kDa. 

Cytochrome c heme lyase, the enzyme responsible for the covalent attachment of heme to cytochrome c, illustrates a second pathway for targeting to the intermembrane space. In this pathway, the Imported protein is delivered directly to the Intermembrane space via the general import pore without Involvement of any Inner-membrane translocation factors... 

Inhibitors of translation - A number of the common inhibitors of prokaryotic translation are also effective in eukaryotic cells. They include pactamycin, tetracycline, and puromycin. Inhibitors that are effective only in eukaryotes include cycloheximide and diphtheria toxin. Cycloheximide inhibits the peptidyltransferase activity of the eukaryotic ribosome. Diphtheria toxin is an enzyme, coded for by a bacteriophage that is lysogenic in the bacterium Corynebacterium diphtheriae. It catalyzes a reaction in which NAD+ adds an ADP ribose group to a specially modified histidine in the translocation factor eEF2, the eukaryotic equivalent of EF-G (Figure 28.36). Because the toxin is a catalyst, minute amounts can irreversibly block a cell s protein synthetic machinery. As a result, pure diphtheria toxin is one of the most deadly substances known. 

Eukaryotic peptide elongation follows similar processes as prokaryotes via aminoacyl-tRNA binding, transpeptidation and translocation, involving the A, P and E sites of the ribosome. Two elongation factors, EFl and EF2 mediate the elongation steps. EFl consists of two components, EFl A equivalent of EF-Tu and EFIB equivalent of EF-Ts. EF2 is the translocation factor that binds GTP and catalyzes hydrolysis of GTP that accompanies translocation. 

Translocation factor (TF) points to the total of PAH that can be transported to the aerial parts of the plant. 

The process of phytoremediation begins with contaminant transport to the plant roots can take up PAH, up taken PAH may be transported, stored, converted, and accumulated in the different cells and tissues of the plant (Marmiroli et al., 2006). To evaluate uptake potential of F. arundinacea and B. curtipendula two concentration factors (root and stem) and translocation factor of three PAH were calculated as shown in Table 1. RCF generally proved to be a good indicator of whether a plant retains a contaminant in the root. 

Table 1. Concentration factors. RCF root concentration factor SCF stem concentration factor TF translocation factor. F. arundinacea (F.a) and R curtipendula (B.c). PHE -phenanthrene PYR-pyrene BaP-benzo[a]pyrene.

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

The anthrax toxin is a tripartite toxin and consists ofthe binding component protective antigen (PA), the lethal factor (LF), which is a metalloprotease, and the edema factor (EF), which is a calmodulin-dependent adenylyl-cyclase. Both enzyme components are translocated via PA into target cells. PA is activated by furin-induced cleavage and forms heptamers, which are similar to the binding components of C2 toxin and iota toxin. In the low pH compartment of endosomes, the heptamers form pores to allow translocation of LF and EF. LF cleaves six of the seven MEKs (MAPK-kinases) thereby inhibiting these enzymes. The functional consequence is the blockade of the MAPK pathways that control cell proliferation, differentiation, inflammation, stress response, and survival. Whether this is the reason for the LT-induced cell death of macrophages is not clear [1]. 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

Cyclosporine A (CsA) is a water-insoluble cyclic peptide from a fungus composed of 11 amino acids. CsA binds to its cytosolic receptor cyclophilin. The CsA/cyclophilin complex reduces the activity of the protein phosphatase calcineurin. Inhibition of this enzyme activity interrupts antigen receptor-induced activation and translocation of the transcription factor NEAT to the nucleus which is essential for the induction of cytokine synthesis in T-lymphocytes. 

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