Serine phosphates

Phosphorylated amino acids move in the order serine phosphate > threonine phosphate > tyrosine phosphate. 

In subsequent years, much evidence has been adduced to support this mechanism. Alkaline phosphatase and, by analogy, other serine enzymes, are directly phosphorylated on serine serine phosphate is not an artifact (Kennedy and Koshland, 1957). In the presence of nitrophenyl acetate, chymotrypsin is acetylated on serine, and the resulting acetylchymotrypsin has been isolated (Balls and Aldrich, 1955 Balls and Wood, 1956). Similarly, the action of p-nitrophenyl pivalate gave rise to pivaloyl chymotrypsin, which could be crystallized (Balls et al., 1957). Neurath and workers showed that acetylchymotrypsin is hydrolyzed at pH 5.5, but that it is reversibly denatured by 8 M urea the denatured derivative is inert to hydrolysis and even to hydroxylamine, whereas the renatured protein, obtained by... 

Figure 5.10 Association of colloidal calcium phosphate (Ca3(P04)2) with the serine phosphate groups of casein (from Schmidt, 1982).

Glimcher, M. J., Krane, S. M. The identification of serine phosphate in enamel proteins. Biochim. Biophys. Acta 90, 477 (1964)... 

The glucose 1-phosphate so formed can be used for ATP synthesis in muscle or converted to free glucose in the liver. Glycogen phosphorylase occurs in two forms the more active phosphorylase a and the less active phosphorylase b (Fig. 6-31). Phosphorylase a has two subunits, each with a specific Ser residue that is phosphorylated at its hydroxyl group. These serine phosphate residues are required for maximal activity of the enzyme. 

In this reaction, phosphorylase a is converted to phosphorylase b by the cleavage of two serine phosphate covalent bonds, one on each subunit of glycogen phosphorylase. 

Figure 3. Effect of pH on the chemical shift of several monoester phosphate compounds. Serine phosphate and inositol monophosphate are in a pure water matrix, and adenosine monophosphate is in a concentrated humic-FeEDTA...

Agren 112) and Engstrom 113) isolated serine phosphate from mammalian alkaline phosphatase that had been incubated with inorganic phosphate in acid pH (<6). Engstrom 114) and Schwartz and Lipmann 35) later obtained similar results with E. coli alkaline phosphatase. They found that a large percentage of the enzyme is phosphorylated, that compounds like glucose 6-phosphate and sodium arsenate inhibit... 

This additive procedure was applied for the study of a number of cases including the interaction of cations with the carrier antibiotics valinomycin 184> and nonac-tin 185), the interaction of CH3NH3+ and (CH3)4N+ with amino acids mimicking the active site of a phosphorylcholine antibody186), the interaction of guanine and cytosine with amino acids 181), the interaction of Ca2+ and Mg2-1- with two serine phosphates 188), and the interaction of the channel-forming antibiotic gramicidin A with different cations 189 191>. 

In the synthesis of casein, serine is incorporated into the protein sequence. Subsequently, some of these serine residues are phosphorylated to form serine phosphate. 

The primary structures (Figures 2, 3 and 4) are given for a-sicasein, 3-casein, and K-casein (1). The most significant aspects of these primary structures are their disproportionate distribution of acidic amino acids, serine phosphate groups and hydrophobic amino acids along the polypeptide chain. 

Samstag, Y, Dreizler, E. M., Ambach, A., Sczakiel, G., Meuer, S. C. (1996). Inhibition of constitutive serine phosphate activity in T lymphoma cells result in phosphorylation of ppl9/cofilin and induces apoptosis./. Immunol. 156, 4167-4173. 

Although one particular serine residue per subunit is phosphoryl-ated during the activation of muscle and liver phosphorylases, this serine phosphate residue may not participate directly in an enzymic... 

The roles of adenosine 5 -phosphate and serine phosphate in the action of muscle phosphorylase are uncertain. The phosphate groups of these two compounds are not believed to participate directly in phosphorylation, because no exchange occurs between these and inorganic phosphate in solution during the degradation of glyco-... 

The C-terminus of a nucleopeptide choline ester 9 was deprotectedt smoothly by butyrylcholine esterase (Scheme 19). Neither the acetate, the N-terminal urethane, the allyl phosphate, the phenylacetamide and the peptide bonds, nor the acid- or base-labile purine nucleosides and serine phosphates are attacked. The methods have been exploited further for the synthesis of several biologically relevant nucleopeptides.t ... 

Phospholipids may consist of a backbone of glycerol esterified with two fatty acids and one molecule of choline phosphate in the position. Tn other phospholipids, the 3 position may be occupied by a molecule of ethanolamine phosphate, serine phosphate, or inositol phosphate. A phospholipid containing choline phosphate is called phosphatidylcholine one containing ethanolamine phosphate is called phosphatidylethanolamine. Generally, the fatty acids esterified as triglycerides contain up to one double bond, whereas those esterified as phos-... 

The most accurate method of analysis for serine, threonine and tyrosine in proteins is to hydrolyze the proteins for several different times (e.g. 24, 48 and 72 hr) and extrapolate the values to 0 time. In general, the more times that are utilized, the more accurate will be the extrapolation. Extrapolation of the NHj content of these hydrolysates to 0 time will also give an estimate of the number of amides present in the protein, if care has been used to exclude NHj during purification of the protein. The inclusion of phenol in the hydrolysates has generally decreased the rates of destruction, particularly for tyrosine. If serine phosphate ( 2.12.4) or similar derivatives are present, the extrapolated curve will be more complex due to different rates of destruction. 

In 1930 Lipmann went back to the Kaiser Wilhelm Institute in Berlin, then to a new institute in Copenhagen in 1932. Between 1931 and 1932, he served as a Rockefeller fellow at the Rockefeller Institute in New York and identified serine phosphate as the constituent of phosphoproteins that contains the phosphate. 

The synthesis of various phosphonate analogues of aspartic acid, glutamic acid and their homologues and serine phosphate have been reported. The kynurenine phosphinic acid analogue 217 and the corresponding phosphinate 218 have been synthesised from iV-protected 2-amino P-propiolactone (Scheme 27). Kinetic resolution was achieved by esterase-selective hydrolysis of the carboxylate group in the diester. 

Hamilton, R., Shute, R.F., Travers, J., Walker, B., and Walker, B.J., A convenient synthesis of phosphonate isosteres of serine phosphates, Tetrahedron Lett., 35, 3597, 1994. 

Halogenoalkyl and Related Acids. In view of their extensive applications as, for example, phosphate mimics, new routes to a-mono- and -di-fluoroalkylphos-phonates are always welcome and during the period of this review a substantial number have been reported. A variety of functionalised examples of such compounds have been prepared from the readily available difluorophosphonate (188). ° For example, the monofluoro analogue (191) of serine phosphate has been synthesised by the reaction of (188) with organocopper reagents to give (190) followed by reduction and further functionalisation (Scheme 28). The... 

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