Dephosphorylation selective

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

Protein phosphorylation-dephosphorylation is a highly versatile and selective process. Not all proteins are subject to phosphorylation, and of the many hydroxyl groups on a protein s surface, only one or a small subset are targeted. While the most common enzyme function affected is the protein s catalytic efficiency, phosphorylation can also alter the affinity for substrates, location within the cell, or responsiveness to regulation by allosteric ligands. Phosphorylation can increase an enzyme s catalytic efficiency, converting it to its active form in one protein, while phosphorylation of another converts it into an intrinsically inefficient, or inactive, form (Table 9—1). 

Flajolet, M., Rakhilin, S., Wang, H. et al. Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. Proc. Natl Acad. Sci. U.S.A. 16006-16011,2003. 

The use of this enzyme in multi-step synthesis is relatively recent. Clapes et al. have reported the first example of FSA-mediated synthesis of iminocyclitols [53]. The synthetic strategy is similar to the one previously described for DHAP-dependent aldolases without the need for the dephosphorylation step. AldoUc reaction of DHA with N-Cbz-3-aminopropanal catalyzed by FSA followed by selective catalytic reductive aminahon furnishes the naturally occurring imino-sugar D-fagomine (Scheme 4.22). 

Entry 7 in Table 3.36 is a rare example of the use of a phosphodiester as a linker for alcohols. This linker, when used in combination with an enzyme-compatible support, can be selectively cleaved with a phosphodiesterase. To obtain the free alcohol, the released phosphate must be subjected to an additional enzymatic dephosphorylation. 

The amount of zinc(II) ions bound to the polymer was quite elegantly determined by the use of a zinc(II) selective fluorophore developed by the same group. [3] Adsorption of phosphates such as 5 -dAMP and 4-NPP, adenosine 3, 5 -cyclic-monophosphate (3, 5 -cAMP) and the corresponding dephosphorylated compounds, deoxyadenosine (dA) and 4-nitrophenol (4-NP) was studied. The polymer was stirred in a solution containing the studied guest in a buffered aqueous solution. The adsorption efficiency was determined by the decrease of the guest molecule concentrations by UV measurement. 

Although CsA and FK506 are extremely selective inhibitors of calcineurin, some of the studies above indicate that these drugs could possibly have calcineurin-independent elfects. Moreover, calcineurin shows phosphatase activity towards a wide variety of phosphoprotein substrates, and inhibition of calcineurin by immunosuppressant-immunophilin complexes blocks phosphatase activity toward a broad spectrum of phos-phoproteins. Inhibitors that blocked calcineurin mediated dephosphorylation of a specific substrate (such as NF-AT, or specific isoforms of NF-AT) without affecting the dephosphorylation of other substrates would be of great therapeutic as well as academic interest. The search for... 

Brooks and Landt (1984) and Brooks (1987) isolated a calmodulin-dependent kinase from rat and bovine mammary acini which selectively phosphorylated dephosphorylated K-casein rather than de-phosphorylated asl-casein or P-casein. 

Studies conducted in our laboratory indicated that profilaggrin was rapidly dephosphorylated during the transition of the mature granular cell into the corneocyte and then underwent selective proteolysis to form lower molecular weight, highly basic species within the SC.50... 

Maxam and Gilbert (1980) have described detailed protocols for the preparation and isolation of dephosphorylated DNA fragments, and reaction schemes for the selective 5 -end and 3 -end labelling of these products either individually or en masse. Pro-... 

This example not only highlights the effect of noncovalent ligand binding on association (and catalysis) but also the role played by covalent phosphorylation and dephosphorylation of selected residues (serine, threonine and tyrosine) in proteins. Phosphorylation/dephosphorylation is an extremely important regulator of the assembly, disassembly and other dynamic properties of many supramolecular structures. 

Pero (5) prepared noncytotoxic stilbene phosphate prodrug derivatives, (V), which were converted into the dephosphorylated cytotoxic drug equivalents, (VI), by action of endothelial enzymes which then acted selectively at the sites of vascular proliferation. 

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