Synthetase kinase

Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Glycogen Synthetase Kinase p56 Lymphoid T Cell Tyrosine Kinase Protein Kinase CK2 (Casein Kinase II)... 

It is thus necessary to confirm the existence of modified cellular function following ligand-receptor or drug-enzyme interaction. Such in vitro experiments, performed on isolated cells, either native or transfected with the protein of interest, can be undertaken for mechanistic and/or therapeutic purposes. The data depicted in Figure 3.10 illustrate the fact that, in HEK293 cells in culture, inhibition of the enzyme glycogen synthetase kinase 3(3 (GSK-3(3) decreases tan protein hyperphosphorylation, one of the anatomopathological hallmarks of Alzheimer s disease, and may thus represent a potential therapeutic approach for this disease. Alternatively, this experimental set-up can also be used for mechanistic purposes to characterize the efficacy of compounds as GSK-3 3 inhibitors. When compared to simple in vitro experiments in which the activity of the purified enzyme is measured in the presence of a... 

Another hormone, namely, insulin, acts in the opposite direction, and produces a rapid rise in glycogen synthetase activity. It has been suggested that insulin acts by changing the glycogen synthetase kinase into a form having a low affinity for cyclic AMP, so that the conversion of the independent into the dependent form (that is, inactivation of the glycogen synthetase) is retarded. 

The antiviral state induced by different types of IFNs is mediated by various IFN-induced proteins. The best-known antiviral effectors produced as a result of IFN cascade induction are shown in Table 2. They include 2 -5 oligoadenylate synthetase (2 -5 OAS), double-stranded RNA activated protein kinase (PKR), and myxovirus (Mx) proteins. Additional effectors include RNA-specific adenosine deaminase 1 (ADARl), the 20-kDa ISG product (ISG20), ISG54 and ISG56, and IFN-stimulated micro RNAs (Pedersen et al. 2007). 

Mitochondria have an outer membrane that is permeable to most metabohtes, an inner membrane that is selectively permeable, and a matrix within (Figure 12-1). The outer membrane is characterized by the presence of various enzymes, including acyl-CoA synthetase and glycerolphosphate acyltransferase. Adenylyl kinase and creatine kinase are found in the intermembrane space. The phospholipid cardiolipin is concentrated in the inner membrane together with the enzymes of the respiratory chain. 

The molecular basis by which interferons promote their characteristic effects, in particular antiviral activity, is understood at least in part. Interferon stimulation of the JAK-STAT pathway induces synthesis of at least 30 different gene products, many of which cooperate to inhibit viral replication. These antiviral gene products are generally enzymes, the most important of which are 2 -5 oligoadenylate synthetase (2,5-A synthetase) and the eIF-2a protein kinase. 

The ability of interferons (especially type I interferons) to induce an antiviral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional interferon actions. The ability of such systems to stall protein synthesis in cells may play a role in interferon-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating interferon-induced anti-proliferative effects on various transformed cells. 

Glutamine synthetase 6.3.1.2 C L-Glutamate NADH ADP Pyruvate Pyruvate kinase Lactate dehydrogenase... 

Classic doubly wound /3 sheets Lactate dehydrogenase domain 1 Alcohol dehydrogenase domain 2 Aspartate transcarbamylase catalytic domain 2 Phosphoglycerate kinase domain 1 Tyrosyl-tRNA synthetase domain 1( )... 

Tyrosyl-tRNA synthetase dl, d2 Thermolysin dl, d2 T4 phage lysozyme dl, d2 Glucosephosphate isomerase dl, d2 Pyruvate kinase dl, d2 Pyruvate kinase d2, d3 Lactate dehydrogenase dl, d2 Alcohol dehydrogenase dl, d2 Glyceraldehyde-phosphate dehydrogenase dl,d2... 

The hypE proteins are 302-376 residues long and appear to consist of three domains. Domain 1 shows sequence identity to a domain from phosphoribosyl-aminoimida-zole synthetase which is involved in the fifth step in de novo purine biosynthesis and to a domain in thiamine phosphate kinase which is involved in the synthesis of the cofactor thiamine diphosphate (TDP). TDP is required by enzymes which cleave the bond adjacent to carbonyl groups, e.g. phosphoketolase, transketolase or pyruvate decarboxylase. Domain 2 also shows identity to a domain found in thiamine phosphate kinase. Domain 3 appears to be unique to the HypF proteins. 

Figure 20.25 Regulation of the activities of the aminoacyl-tRNA synthetases by the concentrations of free tRNAs (i.e. uncharged tRNA). Changes in the concentrations of free tRNAs provide the mechanism for communication between control via the initiation factor (Figure 20.20) and ribosomal protein kinase (steps 6 and 7) and the flux-generating step.

The subsequent cleavage of the thio-ester succinylCoA into succinate and coenzyme A by succinic acid-CoA ligase (succinyl CoA synthetase, succinic thiokinase) is strongly exergonic and is used to synthesize a phosphoric acid anhydride bond ( substrate level phosphorylation , see p. 124). However, it is not ATP that is produced here as is otherwise usually the case, but instead guanosine triphosphate (CTP). However, GTP can be converted into ATP by a nucleoside diphosphate kinase (not shown). 

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